SATB1通过改变核定位调控β-类珠蛋白基因表达
摘要
细胞核是复杂的有机体,包含各种各样动态分布的内容物。但是最新的实验结果显示细胞核其实是有序排布的,即使在有丝分裂的间期当染色质成疏松伸展状态存在时,也并不是想象中那样散乱分布。SKY技术利用不同荧光对不同染色体进行标记并将荧光转为光谱进而用精密仪器进行分析。分析结果显示不同染色体在细胞核内占有特定的空间区域,称为染色体区域。进一步实验分析还指出长时间沉默的基因以及大量的基因荒漠区通常位于染色体区域的内部,而活性表达的基因往往分布在染色体区域的表面,甚至环出,这与染色体间区分布有大量基因表达所需的调控复合物有关,这就是著名的CT-IC模型的基础理论。因此基因在细胞核内的定位就由原来简单分为异染色质区和常染色质区发展得更为深入了,基因在细胞核内的定位以及位置的变化与基因表达调控之间的关系也越来越受到重视。除了基因与自己所处的染色体区域之间的定位关系与基因表达水平有着密切的调控关系,实验还发现,基因与核周边或核中心区域的距离也具有基因表达调控功能。另外核基质作为细胞核内重要的结构,募集了大量与调控相关的转录因子和酶,实验结果发现与核基质的结合状况也与基因活化状况相关。因此基因在细胞核内不是随意排布的,定位往往与基因表达状态息息相关。
众所周知数以万计的基因并不是任何时间或在任何组织中都表达,组织特异性与发育阶段特异性是基因表达的重要特性,也是维持正常个体发育和细胞分化并行使正确功能的保障,无论是基因的表达时间还是组织发生紊乱都会导致细胞功能失常诱发疾病。既然基因的核定位对基因表达存在调控作用,那是否基因的核定位也相应地存在组织特异性和发育阶段特异性昵?实验结果证实了这种假想。基因在核内的定位是随着基因的活化与抑制而动态变化的。处于染色质内部或表面的基因在活化之后会向表面移动或是环出,而原本环出的基因则会在表达水平下降之后环进染色体区域。活性表达的基因往往会远离异染色质区域向常染色质区域靠近,而表达受抑制的基因则会向异染色质区域靠近更是早已发现的现象。基因与核基质的结合其实也是动态变化的,染色质DNA通过许多核基质结合序列与核基质结合,但是并不是所有的这些核基质结合序列都会与核基质结合,而是根据相邻的基因表达状态有选择的结合,而且当基因的表达状况在受到诱导前后发生变化后,与核基质结合的核基质结合序列也会发生变化,这一点也更加证实了核基质并不单纯是固定染色质的核内结构,它与基因的表达调控是密切相关的。
目前对于珠蛋白基因簇在核内的定位调控也有了一些认识,但是并不深入,多是集中在LCR对于β-珠蛋白基因簇核内定位的调控。我们的实验旨在探索珠蛋白基因簇在核内的定位以及该定位与核基质的关系。SATB1蛋白是近几年发现的T细胞特异性表达的核基质结合蛋白,在其它细胞中少有表达。SATB1蛋白可以相互聚合形成鸟笼样结构,并且此笼形结构的形成与和核基质正确结合是密切相关的,这不仅为基因表达调控提供平台,而且介导了基因与核基质的结合,接受核基质上募集的调控因子的调控。有实验发现在人红白血病细胞系K562中过表达SATB1蛋白,可以促进β-珠蛋白基因簇的活化,尤其促进胚胎型的基因表达。主要机理是在β-珠蛋白基因簇LCR区的HS2上以及ε基因的增强子区域有SATB1蛋白的结合位点,因此SATB1蛋白募集的一些去乙酰化抑制酶等染色质修饰蛋白就可以作用于这两点的染色质使其开放,促进基因表达。由于如前所述,SATB1形成的笼形结构可以募集染色质修饰蛋白,而且此作用与核基质密切相关,因此我们假设SATB1蛋白对于珠蛋白基因的调控可能与促使β-珠蛋白基因簇改变核定位有关,而这种核定位的变化有可能与同核基质结合密不可分。
为了证明我们的设想,我们构建了SATB1表达载体以及删除了核基质结合区的突变SATB1的表达载体,并分别转染K562细胞,获得稳定克隆后进行珠蛋白基因簇的定位分析。首先β-类珠蛋白基因的表达水平检测发现,SATB1过表达后可以增加ε基因表达而降低γ基因的表达,这与以前的实验结果吻合。而且与我们预期一致的是,在SATB1突变表达后这种调控结果减弱了。因此提示SATB1对于珠蛋白基因的表达调控可能与核基质的作用相关。然后,我们利用FISH技术观察了SATB1过表达及突变表达的情况下β-珠蛋白基因簇的核内定位情况。先以11号染色体区域为内对照观察,结果发现SATB1过表达后30%的β-珠蛋白基因簇发生了环出,与hemin诱导的K562细胞进行的阳性对照中的37%环出的结果相接近。但是出乎意料的是,在SATB1突变表达后,同样有33%的β-珠蛋白基因簇发生了环出。根据两种情况下珠蛋白基因表达水平的不同以及我们所做的突变分析,这两种情况下的核定位应该是有区别的。于是我们又以核基质进行内对照,对β-珠蛋白基因簇的核定位进行观察。结果发现,在SATB1过表达时,大部分β-珠蛋白基因簇是与核基质结合的,而当SATB1突变表达之后,虽然β-珠蛋白基因簇发生了环出,但是并不与核基质结合,而是处于核晕的部位。这与以往的实验发现用红系不表达的IgG基因簇上的LCR替代β-珠蛋白基因簇原位的LCR之后虽然促使了珠蛋白基因簇的环出,但是并不能转位使其远离异染色质区也不能促进珠蛋白基因的表达有相似之处。因此提示,β-珠蛋白基因簇的环出是调控珠蛋白基因表达的必要非充分条件,环出之后的具体定位也起重要作用。
另外由于核基质有多种转录调节因子结合,那么与核基质的不同结合状态是否会改变β-珠蛋白基因簇与重要反式因子的结合状况?我们利用ChIP技术观察β-珠蛋白基因簇与PolⅡ与GATA1的结合状态。结果发现,SATB1过表达后增加了HS2区域和ε基因的启动子区与PolⅡ的结合几率,同时降低了γ基因的启动子区与PolⅡ的结合几率。而在SATB1突变表达的情况下,三个观察点上的PolⅡ结合几率与正常K562细胞对照没有明显差别。关于GATA1,实验发现SATB1过表达后增加了HS2区域和GATA1的结合几率,但是降低了ε基因和γ基因GATA1结合位点的结合几率;而在SATB1突变表达的情况下,HS2区域和GATA1的结合几率降低了,ε基因与GATA1的结合几率没有明显规律,而γ基因的结合情况与正常对照没有差别.此结果与半定量PCR发现的正常SATB1蛋白促进胚胎期珠蛋白基因表达而降低胎儿期珠蛋白基因表达,突变SATB1蛋白不具有此调控效果的结果相一致,也提示SATB1蛋白可能通过介导β-珠蛋白基因簇与核基质的结合,改变与调控因子的结合状态从而调控珠蛋白基因表达。
基于我们的研究,我们提出关于SATB1调控β-珠蛋白基因簇机制模型的假想:SATB1蛋白相互聚合形成笼形结构,在聚合过程中促使与之结合的β-珠蛋白基因簇环出11号染色体区域,并且介导β-珠蛋白基因簇与核基质的结合。并且由于SATB1蛋白的结合位点主要是在HS2区域和ε基因的近端调控元件,因此在与SATB1蛋白结合的过程中促进了LCR与ε基因的结合,增强了ε基因的表达,而ε基因与γ基因之间对于LCR的竞争导致了LCR对γ基因的增强减少,导致γ基因表达降低。
The nucleus is a compartmentalized organelle;the localization of many genes in the nucleus is specific.Understanding the basic principles of nuclear architecture and the changes in nuclear organization is important to study the profound differences in gene activities established and maintained to ensure the development and function of a complex organism.Every single chromosome occupies a certain territory in nucleus,with smaller one situating towards the interior and larger one towards the periphery.Gene content is also a key determinant of CT positioning.The nucleus also contains a largely chromatin-free space lined by chromatin-domain surfaces.A ribonucleo-protein network is located in this space.These non-chromatin domains may represent storage sites of proteins or protein complexes.The CT-IC model hypnotizes that partial transcription complexes are pre-established in the IC to fulfill its role as a functionally defined compartment; Regulatory and coding sequences of these active genes can interact with the transcription machinery only when they are positioned at the surface of chromatin domains that line the IC,or on chromatin loops that extend into the IC;Long-term or permanently silenced genes should be located within the interior of compact chromatin domains that are nonaccessible to the transcription machinery.In more general terms,genes that require long-term silencing should be physically separated from permanently active genes to an extent that allows their positioning in different chromatin compartments.
Nuclear organization may be cell type-specific,because the chromatin organization was found to be similar in cells from the same cell linage and maintained during cell division.Co-regulated gene clusters may be proximally positioned to facilitate their regulation through the creation of expression hubs with shared concentrations of regulatory proteins.The combined effect of the association of domains from throughout the genome would yield a cell-specific nuclear topology,resulting in definable patterns of chromosome organization.Nuclear organization may be also developmentally specific.Recent studies suggested that many genes had the ability to mobilize to specific locations within the interphase nucleus according to their state of transcription during development.
As for theβ-globin locus,the nuclear relocation has been realized to be one of the mechanisms in the regulation of expression.It was reported that moving away from centromeric heterochromatin is essential for the activation ofβ-globin locus;and extrusion from the chromosomal territory in the interphase nucleus is associated with high level expression ofβ-like globin genes.Both cis-regulatory elements and transacting proteins have been implied involved in the repositioning ofβ-globin locus.But the complex mechanism is far from clear and other factors participating in the relocation ofβ-globin locus need elucidating.
The nuclear matrix,composed of lamin and internal network made of proteins and RNAs,can organize nuclear structure by attaching with chromatin periodically. Additionally,this attachment is mobile and associated with the expression state of related genes.So the nuclear matrix is one of the factors that regulate the position of genes according to its expression activity.Furthermore,a MAR binding protein-SATB1 was lately found to improve embryonicβ-like globin gene expression in K562 cells.SATB1 proteins can form cage-like structure and provide a regulatory platform for genes,and this structure is associated with the nuclear matrix.Though the previous study suggested that SATB1 regulatesβ-like globin genes through remodeling chromatin,we assume that SATB1 may also play regulatory role in the level of nuclear structure and the regulation of relocation may be related with nuclear matrix.
We constructed normal and mutant(with matrix binding domain deleted) SATB1 expression vectors,and transfected them into K562 cells.Different primers were designed to confirm the expression of both endogenous and exogenous,both normal and mutant SATB1.Western Blot was applied to detect the expression in the protein level.After the construction of SATB1/K562 cells and m SATB1/K562 cells,the expression level of[3-like globin genes were detected by RT-PCR.The results showed that SATB1 over expression increasedεglobin gene expression and decreasedγ-globin gene expression,leavingβ-globin gene still not expressed,which is consistent with the previous results.But the mutant SATB1 didn't have this regulatory effect,suggesting the regulatory mechanism of SATB1 is associated with nuclear matrix.DNA FISH exploring the nuclear location ofβ-globin locus showed that both normal SATB1 and mutant SATB1 could induceβ-globin locus to loop out of chromosomal territory,but only the normal SATB1 can anchor the locus on the nuclear matrix.We also detcted that binding situation ofβ-globin locus with transacting factors by ChIP assay using the antibodies to PolⅡand GATA1.The results showed that over expression of normal SATB1 increased the binding of HS2 core sequence andε-globin gene promoter with RNAPolⅡand decreased the binding ofε-globin gene upstream regulatory elements with GATA1,while the mutant SATB1 didn't.The results suggested that anchoring with the nuclear matrix is important for the proper binding situation to improve the expression ofεglobin gene.
Based on our and previous results,we proposed that SATB1 regulatingβ-1ike globin genes is a multi-step process.SATB1 proteins form cage-like structure,inducing the associatedβ-globin locus loop out of CT and anchored it on the nuclear matrix.Because the binding sites of SATB1 locate in the HS2 andεgene promoter,the regulatory factors on the nuclear matrix mainly affect the chromatin of the LCR andε-globin gene.But the relocation is the first step of regulation;it brings not only direct effect but also the regulation of next step.During binding with SATB1,the LCR andε-globin gene interact with each other.LCR causes the further opening of the chromatin nearε-globin gene and enhances the expression ofε-globin gene.In K562 cells,bothε-globin gene and T globin gene have the potential to express,and compete for the LCR.SATB1 improve the interaction between LCR andε-globin gene,the competition mechanism will decrease the interaction between LCR andγ-globin gene and cause the decreae of theγ-globin gene expression.In conclusion,our results suggested thatβ-like globin genes are regulated by SATB1 through relocating the cluster in the nuclear;and looping out of the chromosomal territory is necessary but not suffitient forβ-like globin genes regulation,attachment with nuclear matrix is also very important.Furthermore,SATB1 regulatesβ-like globin genes in all the levels of DNA,chromatin and nuclear organization.
众所周知数以万计的基因并不是任何时间或在任何组织中都表达,组织特异性与发育阶段特异性是基因表达的重要特性,也是维持正常个体发育和细胞分化并行使正确功能的保障,无论是基因的表达时间还是组织发生紊乱都会导致细胞功能失常诱发疾病。既然基因的核定位对基因表达存在调控作用,那是否基因的核定位也相应地存在组织特异性和发育阶段特异性昵?实验结果证实了这种假想。基因在核内的定位是随着基因的活化与抑制而动态变化的。处于染色质内部或表面的基因在活化之后会向表面移动或是环出,而原本环出的基因则会在表达水平下降之后环进染色体区域。活性表达的基因往往会远离异染色质区域向常染色质区域靠近,而表达受抑制的基因则会向异染色质区域靠近更是早已发现的现象。基因与核基质的结合其实也是动态变化的,染色质DNA通过许多核基质结合序列与核基质结合,但是并不是所有的这些核基质结合序列都会与核基质结合,而是根据相邻的基因表达状态有选择的结合,而且当基因的表达状况在受到诱导前后发生变化后,与核基质结合的核基质结合序列也会发生变化,这一点也更加证实了核基质并不单纯是固定染色质的核内结构,它与基因的表达调控是密切相关的。
目前对于珠蛋白基因簇在核内的定位调控也有了一些认识,但是并不深入,多是集中在LCR对于β-珠蛋白基因簇核内定位的调控。我们的实验旨在探索珠蛋白基因簇在核内的定位以及该定位与核基质的关系。SATB1蛋白是近几年发现的T细胞特异性表达的核基质结合蛋白,在其它细胞中少有表达。SATB1蛋白可以相互聚合形成鸟笼样结构,并且此笼形结构的形成与和核基质正确结合是密切相关的,这不仅为基因表达调控提供平台,而且介导了基因与核基质的结合,接受核基质上募集的调控因子的调控。有实验发现在人红白血病细胞系K562中过表达SATB1蛋白,可以促进β-珠蛋白基因簇的活化,尤其促进胚胎型的基因表达。主要机理是在β-珠蛋白基因簇LCR区的HS2上以及ε基因的增强子区域有SATB1蛋白的结合位点,因此SATB1蛋白募集的一些去乙酰化抑制酶等染色质修饰蛋白就可以作用于这两点的染色质使其开放,促进基因表达。由于如前所述,SATB1形成的笼形结构可以募集染色质修饰蛋白,而且此作用与核基质密切相关,因此我们假设SATB1蛋白对于珠蛋白基因的调控可能与促使β-珠蛋白基因簇改变核定位有关,而这种核定位的变化有可能与同核基质结合密不可分。
为了证明我们的设想,我们构建了SATB1表达载体以及删除了核基质结合区的突变SATB1的表达载体,并分别转染K562细胞,获得稳定克隆后进行珠蛋白基因簇的定位分析。首先β-类珠蛋白基因的表达水平检测发现,SATB1过表达后可以增加ε基因表达而降低γ基因的表达,这与以前的实验结果吻合。而且与我们预期一致的是,在SATB1突变表达后这种调控结果减弱了。因此提示SATB1对于珠蛋白基因的表达调控可能与核基质的作用相关。然后,我们利用FISH技术观察了SATB1过表达及突变表达的情况下β-珠蛋白基因簇的核内定位情况。先以11号染色体区域为内对照观察,结果发现SATB1过表达后30%的β-珠蛋白基因簇发生了环出,与hemin诱导的K562细胞进行的阳性对照中的37%环出的结果相接近。但是出乎意料的是,在SATB1突变表达后,同样有33%的β-珠蛋白基因簇发生了环出。根据两种情况下珠蛋白基因表达水平的不同以及我们所做的突变分析,这两种情况下的核定位应该是有区别的。于是我们又以核基质进行内对照,对β-珠蛋白基因簇的核定位进行观察。结果发现,在SATB1过表达时,大部分β-珠蛋白基因簇是与核基质结合的,而当SATB1突变表达之后,虽然β-珠蛋白基因簇发生了环出,但是并不与核基质结合,而是处于核晕的部位。这与以往的实验发现用红系不表达的IgG基因簇上的LCR替代β-珠蛋白基因簇原位的LCR之后虽然促使了珠蛋白基因簇的环出,但是并不能转位使其远离异染色质区也不能促进珠蛋白基因的表达有相似之处。因此提示,β-珠蛋白基因簇的环出是调控珠蛋白基因表达的必要非充分条件,环出之后的具体定位也起重要作用。
另外由于核基质有多种转录调节因子结合,那么与核基质的不同结合状态是否会改变β-珠蛋白基因簇与重要反式因子的结合状况?我们利用ChIP技术观察β-珠蛋白基因簇与PolⅡ与GATA1的结合状态。结果发现,SATB1过表达后增加了HS2区域和ε基因的启动子区与PolⅡ的结合几率,同时降低了γ基因的启动子区与PolⅡ的结合几率。而在SATB1突变表达的情况下,三个观察点上的PolⅡ结合几率与正常K562细胞对照没有明显差别。关于GATA1,实验发现SATB1过表达后增加了HS2区域和GATA1的结合几率,但是降低了ε基因和γ基因GATA1结合位点的结合几率;而在SATB1突变表达的情况下,HS2区域和GATA1的结合几率降低了,ε基因与GATA1的结合几率没有明显规律,而γ基因的结合情况与正常对照没有差别.此结果与半定量PCR发现的正常SATB1蛋白促进胚胎期珠蛋白基因表达而降低胎儿期珠蛋白基因表达,突变SATB1蛋白不具有此调控效果的结果相一致,也提示SATB1蛋白可能通过介导β-珠蛋白基因簇与核基质的结合,改变与调控因子的结合状态从而调控珠蛋白基因表达。
基于我们的研究,我们提出关于SATB1调控β-珠蛋白基因簇机制模型的假想:SATB1蛋白相互聚合形成笼形结构,在聚合过程中促使与之结合的β-珠蛋白基因簇环出11号染色体区域,并且介导β-珠蛋白基因簇与核基质的结合。并且由于SATB1蛋白的结合位点主要是在HS2区域和ε基因的近端调控元件,因此在与SATB1蛋白结合的过程中促进了LCR与ε基因的结合,增强了ε基因的表达,而ε基因与γ基因之间对于LCR的竞争导致了LCR对γ基因的增强减少,导致γ基因表达降低。
The nucleus is a compartmentalized organelle;the localization of many genes in the nucleus is specific.Understanding the basic principles of nuclear architecture and the changes in nuclear organization is important to study the profound differences in gene activities established and maintained to ensure the development and function of a complex organism.Every single chromosome occupies a certain territory in nucleus,with smaller one situating towards the interior and larger one towards the periphery.Gene content is also a key determinant of CT positioning.The nucleus also contains a largely chromatin-free space lined by chromatin-domain surfaces.A ribonucleo-protein network is located in this space.These non-chromatin domains may represent storage sites of proteins or protein complexes.The CT-IC model hypnotizes that partial transcription complexes are pre-established in the IC to fulfill its role as a functionally defined compartment; Regulatory and coding sequences of these active genes can interact with the transcription machinery only when they are positioned at the surface of chromatin domains that line the IC,or on chromatin loops that extend into the IC;Long-term or permanently silenced genes should be located within the interior of compact chromatin domains that are nonaccessible to the transcription machinery.In more general terms,genes that require long-term silencing should be physically separated from permanently active genes to an extent that allows their positioning in different chromatin compartments.
Nuclear organization may be cell type-specific,because the chromatin organization was found to be similar in cells from the same cell linage and maintained during cell division.Co-regulated gene clusters may be proximally positioned to facilitate their regulation through the creation of expression hubs with shared concentrations of regulatory proteins.The combined effect of the association of domains from throughout the genome would yield a cell-specific nuclear topology,resulting in definable patterns of chromosome organization.Nuclear organization may be also developmentally specific.Recent studies suggested that many genes had the ability to mobilize to specific locations within the interphase nucleus according to their state of transcription during development.
As for theβ-globin locus,the nuclear relocation has been realized to be one of the mechanisms in the regulation of expression.It was reported that moving away from centromeric heterochromatin is essential for the activation ofβ-globin locus;and extrusion from the chromosomal territory in the interphase nucleus is associated with high level expression ofβ-like globin genes.Both cis-regulatory elements and transacting proteins have been implied involved in the repositioning ofβ-globin locus.But the complex mechanism is far from clear and other factors participating in the relocation ofβ-globin locus need elucidating.
The nuclear matrix,composed of lamin and internal network made of proteins and RNAs,can organize nuclear structure by attaching with chromatin periodically. Additionally,this attachment is mobile and associated with the expression state of related genes.So the nuclear matrix is one of the factors that regulate the position of genes according to its expression activity.Furthermore,a MAR binding protein-SATB1 was lately found to improve embryonicβ-like globin gene expression in K562 cells.SATB1 proteins can form cage-like structure and provide a regulatory platform for genes,and this structure is associated with the nuclear matrix.Though the previous study suggested that SATB1 regulatesβ-like globin genes through remodeling chromatin,we assume that SATB1 may also play regulatory role in the level of nuclear structure and the regulation of relocation may be related with nuclear matrix.
We constructed normal and mutant(with matrix binding domain deleted) SATB1 expression vectors,and transfected them into K562 cells.Different primers were designed to confirm the expression of both endogenous and exogenous,both normal and mutant SATB1.Western Blot was applied to detect the expression in the protein level.After the construction of SATB1/K562 cells and m SATB1/K562 cells,the expression level of[3-like globin genes were detected by RT-PCR.The results showed that SATB1 over expression increasedεglobin gene expression and decreasedγ-globin gene expression,leavingβ-globin gene still not expressed,which is consistent with the previous results.But the mutant SATB1 didn't have this regulatory effect,suggesting the regulatory mechanism of SATB1 is associated with nuclear matrix.DNA FISH exploring the nuclear location ofβ-globin locus showed that both normal SATB1 and mutant SATB1 could induceβ-globin locus to loop out of chromosomal territory,but only the normal SATB1 can anchor the locus on the nuclear matrix.We also detcted that binding situation ofβ-globin locus with transacting factors by ChIP assay using the antibodies to PolⅡand GATA1.The results showed that over expression of normal SATB1 increased the binding of HS2 core sequence andε-globin gene promoter with RNAPolⅡand decreased the binding ofε-globin gene upstream regulatory elements with GATA1,while the mutant SATB1 didn't.The results suggested that anchoring with the nuclear matrix is important for the proper binding situation to improve the expression ofεglobin gene.
Based on our and previous results,we proposed that SATB1 regulatingβ-1ike globin genes is a multi-step process.SATB1 proteins form cage-like structure,inducing the associatedβ-globin locus loop out of CT and anchored it on the nuclear matrix.Because the binding sites of SATB1 locate in the HS2 andεgene promoter,the regulatory factors on the nuclear matrix mainly affect the chromatin of the LCR andε-globin gene.But the relocation is the first step of regulation;it brings not only direct effect but also the regulation of next step.During binding with SATB1,the LCR andε-globin gene interact with each other.LCR causes the further opening of the chromatin nearε-globin gene and enhances the expression ofε-globin gene.In K562 cells,bothε-globin gene and T globin gene have the potential to express,and compete for the LCR.SATB1 improve the interaction between LCR andε-globin gene,the competition mechanism will decrease the interaction between LCR andγ-globin gene and cause the decreae of theγ-globin gene expression.In conclusion,our results suggested thatβ-like globin genes are regulated by SATB1 through relocating the cluster in the nuclear;and looping out of the chromosomal territory is necessary but not suffitient forβ-like globin genes regulation,attachment with nuclear matrix is also very important.Furthermore,SATB1 regulatesβ-like globin genes in all the levels of DNA,chromatin and nuclear organization.
引文
Alvarez, J.D. et al. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev. 14, 521-535 (2000).
Ashe HL, Monks J, & Wijgerde M. Intergenic transcription and transinduction of the human beta-globin locus. Genes Dev. 11, 2494-509. (1997)
Belmont, A. Curr. Opin. Cell Biol. 15, 304 (2003).
Berezney, R. & Wei, X. The new paradigm: integrating genomic function and nuclear architecture. J. Cell. Biochem. 31, S238-S242 (1998).
Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3,207-217(1999).
Bulger, M., et al. ChIPs of the β-globin locus: unraveling gene regulation within an active domain. Curr. Opin. Genet. Dev. 12, 170-177. (2002)
Bungert J., et al. Synergistic regulation of human β-globin gene switching by locus control region elements HS3 and HS4. Genes Dev. 9: 3083-3096. (1995)
Cai, S. & Kohwi-Shigematsu, T. Intranuclear relocalization of matrix binding sites during T cell activation detected by amplified fluorescence in situ hybridization. Methods 19, 394-402 (1999).
Cai, S., Han, H.J., & Kohwi-Shigematsu, T. Tissue-specific nuclear architecture and gene expession regulated by SATB1. nature genetics. 34. 42-52,(2003).
Carter, D., et al. Long-range chromatin regulatory interactions in vivo. Nat Genet.32, 623-6. (2002)
Chambeyron, S. & Bickmore, W. A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription Genes Dev. 18, 1119 (2004).
Chen, H., R.J. Lin, W. Xie, D. Wilpitz, & R.M. Evans. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell 98: 675-686. (1999)
Chien, C.T., S. Buck, R. Sternglanz & D. Shore. Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast. Cell. 75, 531-541. (1993)
Cockerill,P.N. & Garrard,W.T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell, 44, 273-282.(1986)
Cremer T.&Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature, 2, 292-301(2001).
Cremer, T. et al. Chromosome territories, interchromatin domain compartment and nuclear matrix. An integrated view of the functional nuclear architecture. Crit. Rev. Eukaryotic Gene Expression 12, 179-212 (2000).
Cremer, T., Dietzel, S., Eils, R., Lichter, P. & Cremer, C. in Kew Chromosome Conference IV (ed. Benett, M. D.) 63-81 (Royal Botanic Gardens, Kew), (1995)
de Belle, I., Cai, S. & Kohwi-Shigematsu, T. The genomic sequences bound to special AT-rich sequence-binding protein 1 (SATB1) in vivo in Jurkat T cells are tightly associated with the nuclear matrix at the bases of the chromatin loops. J. Cell Biol. 141, 335-348 (1998).
Deisserroth, A., et al. Localization of the human α-globin structural gene to chromosome16 in somatic cell hybrids by molecular hybridization assay, Cell. 12: 205-218.(1977)
Desserroth, A., et al. Chromosomal localization of human β-globin gene on human chromosome 11 in somatic cell hybrids. Proc. Natl. Acad. Sci. USA. 1978, 75:1456-1460. (2001)
Dickinson, L.A., Joh, T., Kohwi, Y. & Kohwi-Shigematsu, T. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell 70, 631-645 (1992).
Evans T, Felsenfeld G & Reitman M. Control of globin gene transcription. Annual Review in Cell Biology. 6, 95-124. (1990)
Forrester, W.C., et al. A developmentally stable chromatin structure in the human β-globin gene cluster, Proc. Natl. Acad. Sci. USA. 83: 1359-1363. (1986)
Galiova, G., et al. Nuclear topography of h-like globin gene cluster in IL-3-stimulated human leukemic K-562 cells.Blood Cells, Molecules, and Diseases 33 4 - 14 (2004).
Gong, Q.H., et al.,Transcriptional role of a conserved GATA-1 site in the human ε-Globin Gene Promoter. Mol. Cell. Bio.,11, 2558-2566, (1991)
Gotta, M. & S.M. Gasser. Nuclear organization and transcriptional silencing in yeast. Experientia 52: 1136-1147.(1996)
Gribnau, J., et al. Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Mol Cell. 5, 377-86. (2000)
Grosveld, F., et al. Position-independent, high-level expression of the human β-globin gene in transgenic mice. Cell. 1987, 51: 975-985.
Grosveld, F., et al The regulation of human globin gene switching. Philos. Trans. R. Soc. Lond. Ser. B 339, 183-191. (1993)
Gruenbaum Y, Goldman RD, Meyuhas R, Mills E, Margalit A, Fridkin A, Dayani Y, Prokocimer M, Enosh A. The nuclear lamina and its functions in the nucleus. Int Rev Cytol 226, 1-62.(2003)
Gui C. & Dean A. Acetylation of a specific promoter nucleosome accompanies activation of the ε-globin gene by β-globin locus control region HS2. Mol. Cell. Bio. 21, 1155-1163.(2001)
Heng, H. H. Q. et al, Chromatin loops are selectively anchored using scaffold/matrix-attachment regions. J. of Cell Sci. 117,999-1008,(2004).
Jackson, D. Understanding nuclear organization: when information becomes knowledge. EMBO reports 6, 213-217. (2005).
Jenuwein T, & Allis CD. Translating the histone code. Science. 293. 1074-80. (2001)
Karlsson S & Nienhuis A. Developmental regulation of human globin genes, Annual Review in Biochemistry 54. 1071-1108. (1985)
Kosak, S. T.& Groudine, M. Gene order and dynamic domains. Science, 22, 644-647 (2004).
Larovaia, O. V. et al Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix. Nucleic Acids Research, 33, 4157-4163 (2005)
Li Q., Harju S. & Peterson K.R. Locus control regions: coming of an age at a decade plus Trends Genet. 15. 403-408(1999)
Litt, M.D., et al. Correlation between histone lysine methylation and developmental changes at the chicken β-globin locus. Science a 293. 2453-2455. (2001)
Litt, M.D., et al. Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci. EMBO J. b 20. 2224-2235.(2001)
Maillet, L., C. Boscheron, M. Gotta, S. Marcand, E. Gilson, and S.M. Gasser. Evidence for silencing compartments within the yeast nucleus: A role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes & Dev. 10: 1796-1811. (1996).
Matera, A. G. Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol. 9, 302-309 (1999).
Milot, E., et al. Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription. Cell 87, 105-114.(1996)
Misteli, T. Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function. J. Cell Sci. 113, 1841-1849 (2000).
Mounkes LC, Stewart CL Aging and nuclear organization: lamins and progeria. Curr Opin Cell Biol 16: 322-327.(2004)
Munkel, C. et al. Compartmentalization of interphase chromosomes observed in simulation and experiment. J. Mol. Biol. 285, 1053-1065 (1999).
Nickerson, J. A. Experimental observations of a nuclear matrix. J. Cell Sci. 114, 463-474 (2001).
Noma K, Allis CD, & Grewal SI. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science. 293.5532.(2001)
O'Neill, L.P. and B.M. Turner. Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner. EMBO J. 14: 3946-3957.( 1995).
Parekh, B.S. and T. Maniatis. Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFNbeta promoter. Mol. Cell 3: 125-129. (1999).
Pikaart M.J., Recillas-Targa F., & Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators. Genes Dev. 12: 2852-2862. (1998)
Pitot, H. C. et al. A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors. Clin. Cancer Res. 8, 712-717 (2002).
Ragoczy, T., et al. A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements. Chromosome Research, 11, 513-525, (2003).
Raich, N., et al. GATAI and YY1 are developmental repressors of the human s-globin gene. The EMBO J. 14, 801-809, (1995)
Schubeler D, et al, Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human b-globin locus. Genes & Dev. 14, 940-950, (2000).
Schubeler D., Francastel C, Cimbora D.M., et al. Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human 3 -globin locus. Genes Dev 14: 940-950. (2000)
Schwartz, G. H. et al. A phase I study of bizelesin, a highly potent and selective DNA-interactive agent, in patients with advanced solid malignancies. Ann. Oncol. 14, 775-782 (2003).
Seo, J., Lozano, M.M. & Dudley, J. P. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J. of Bio. Chem. 280, 24600-24609, (2005).
Sun ZW, & Allis CD. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature. 418(6893): 104-8. (2002)
Townes, T.M. & Behringer R.R. Human globin locus activation region (LAR): role in temporal control. Trends Genet. 6, 219-223. (1990)
Tuan D, Solomon W, Li Q, et al. The "β-like globin " gene domain in human erythroid cells, Proc. Natl. Acad. Sci. USA. 82: 6384-6388.(1985)
Visser, A. E., Jaunin, F., Fakan, S. & Aten, J. A. High resolution analysis of interphase chromosome domains. J. Cell Sci. 113, 2585-2593 (2000).
Volpi, E. V. et al., J. Cell Sci. 113, 1565 (2000).
Wang, J. et al., J. Cell Biol. 164, 515 (2004).
Wijgerde N., Grosveld F., & Fraser P. Transcription complex stability and chromatin dynamics in vivo. Nature. 377. 209-213 (1995)
Wilson C.J., Chao D.M., Imbalzano A.N., et al. RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling, Cell, 84: 235-244, (1996) .
Wittschieben B.O., Otero G., Bizemont T.D., Fellows J., et al. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme, Mol. Cell, 1: 123-128. (1999)
Woynarowski, J. M. AT islands- their nature and potential for anticancer strategies. Curr. Cancer Drug Targets 4,219-234 (2004).
Yasui, D., et al SATB1 targets chromatin remodelling to regulate genes over long distances. Nature, 419 641-645,(2002).
Yeh, T.Y., Chuang, J.Z.& Sung, Ch.H. Dynein light chain rp3 acts as a nuclear matrixassociated transcriptional modulator in a dyneinindependent pathway. J. of Cell Sci. 118,3431-3443,(2005).
Zink, D., Fischer, A.H.& Nickerson, J. A. Nuclear structure in cancer cells.Nature reviews, 4, 677-687,(2004)
[1] Levine, M. and Tjian, R. (2003): 'Transcription regulation and animal diversity.', Nature, 424, pp. 147-51
[2] Desset, S. and Vaury, Ch. (2005): 'Transcriptional interference mediated by retrotransposons within the genome of their host: lessons from alleles of the white gene from Drosophila melanogaster', Cytogenetic and Genome Research, 110, pp. 209-214
[3] Howard, M.L.and Davidson, E.H. (2004): 'cis-Regulatory control circuits in development', Dev Biol. 271, pp. 109-118
[4] Lander,E.S. et al , (2001) : 'Initial sequencing and analysis of the human genome', Nature. 409, pp. 860-921
[5] Graveley, B.R. (2001): 'Alternative splicing: increasing diversity in the proteomic world', Trends. Genet. 17, pp. 100-107
[6] Baltimore, D. (2001): 'Our genome unveiled', Nature, 409, pp.814-6
[7] Ruvkun,G. and Hobert,O. (1998): 'The taxonomy of developmental control in Caenorhabditis elegans', Science, 282, pp.2033-2041
[8] Aoyagi, N. and Wassarman, D.A. (2000): 'Genes encoding Drosophila melanogaster RNA polymerase II general transcription factors: diversity in TFIIA and TFIID components contributes to gene-specific transcriptional regulation', J. Cell Biol. .150, pp.F45-50
[9] Wyrick, J.J.and Young, R.A. (2002): 'Deciphering gene expression regulatory networks', Curr. Opin. Genet. Dev., 12, pp. 130-136
[10] Okada, N. and Takeda, J. (2004): 'Biological significance in transposon-mediated mutation and molecular evolution-special reference to the junk DNA', Tanpakushitsu Kakusan Koso., 49, pp. 2075-2079
[11] Bowen, N.J. and Jordan, I.K. (2002): ' Transposable elements and the evolution of eukaryotic complexity', Curr. Issues Mol. Biol., 4, pp.65-76
[12] Conte, C., Dastugue, B. and Vaury, C. (2002): 'Coupling of enhancer and insulator properties identified in two retrotransposons modulates their mutagenic impact on nearby genes', Mol. Cell Biol., 22, pp. 1767-1777
[13] Miller, W.J., McDonald, J.F., Nouaud, D. and Anxolabehere, D. (1999): 'Molecular domestication - more than a sporadic episode in evolution', Genetica, 107, pp.197-207
[14] Desset, S. and Vaury, Ch., (2005): 'Transcriptional interference mediated by retrotransposons within the genome of their host: lessons from alleles of the white gene from Drosophila melanogaster', Cytogenetic and Genome Research, 110, pp.209-214
[15] Iglesias, A.R., Kindlund, E., Tammi, M. and Wadelius, C. (2004): 'Some microsatellites may act as novel polymorphic cis-regulatory elements through transcription factor binding', Gene, 341, pp.149-165
[16] Lopez, R.A., Schoetz, S. DeAngelis, K., 'Neill, D.O. and Bank, A. (2002): 'Multiple hematopoietic defects and delayed globin switching in Ikaros null mice', Proc. Natl. Acad. Sci U S A, 99, pp.602-607
[17] Pastinen, T. and Hudson, T.J. (2004): 'Cis-acting regulatory variation in the human genome', Scienc,.306, pp.647-650
[18] Weber, J.L. and Wong, C. (1993): 'Mutation of human short tandem repeats', Hum. Mol. Genet., 2, pp.1123-1128
[19] Pastinen, T. et al (2004): 'A survey of genetic and epigenetic variation affecting human gene expression', Physiol. Genomics, 16, pp. 184-193
[20] Knight, J.C., Keating, B.J., Rockett, K.A. and Kwiatkowski, D.P. (2003): 'In vivo characterization of regulatory polymorphisms by allele-specific quantification of RNA polymerase loading', Nat. Genet., 33, pp.469-475
[21] Knight, J.C., Keating, B.J. and Kwiatkowski, D.P. (2004): 'Allele-specific repression of lymphotoxin-alpha by activated B cell factor-1', Nat. Genet., 36, pp.394-399
[22] Hudson, T.J. (2003): 'Wanted: regulatory SNPs', Nat. Genet., 33, pp.439-440
[23] Takada, S. et al (2002): 'Epigenetic analysis of the Dlkl-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19', Hum. Mol. Genet, 11, pp.77-86
[24] Ferguson-Smith, A.C. (2000): 'Genetic imprinting: silencing elements have their say', Curr. Biol., 10, pp. R872-875
[25] Fedoriw, A.M., Stein, P., Svoboda, P. Schultz, R.M. and Bartolomei, M.S. (2004): 'Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting', Science, 303, pp.238-240
[26] Guo, L., Hu-Li, J. and Paul, WE. (2005): 'Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13', Immunity, 23, pp.89-99
[27] Avner, P. and Heard, E. (2001): 'X-chromosome inactivation: counting, choice and initiation', Nat. Rev. Genet., 2, pp. 59-67
[28] Jeannie, T.L Regulation of X-chromosome counting by Tsix and Xite sequences. Science, 309,29, 768-771,2005
[29] Steven, T. K. and Groudine, M. (2004): 'Gene Order and Dynamic Domains', Science, 306, pp.644-647
[30] Kosak, S.T. and Groudine M. (2004): 'Form follows function: The genomic organization of cellular differentiation', Genes. Dev., 18, pp. 1371-1384
[31] Cheutin, T., McNairn, A.J., Jenuwein, T., Gilbert, D.M., Singh, P.B. and Misteli, T. (2003): 'Maintenance of stable heterochromatin domains by dynamic HP1 binding', Science, 299, pp.721-725
[32] Chambeyron, S. and Bickmore, W. A. (2004): 'Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription', Gene. Dev., 18, pp.1119 - 1130
[33] Kosak, S.T. and Groudine, M. (2004): 'Form follows function: the genomic organization of cellular differentiation', Gene. Dev., 18, pp.1371 - 1384
[34] Cremer, T. and Cremer, C. (2001); 'Chromosome territories, nuclear architecture and gene regulation in mammalian cells', Nat. Rev. Genet., 2, pp.292-301
[35] Schubeler, D., Francastel, C, Cimbora, D.M., Reik, A., Martin, D.I. and Groudine, M. (2000): 'Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta-globin locus', Genes Dev., 14, pp.940-95,.
[36] Ragoczy, T., Telling, A., Sawado, T., Groudine, M. and Kosak, S.T. (2003): 'A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements', Chromosome Res., 11, pp.513-525
[37] Kuhn, E.J. and Geyer, P.K. (2003): 'Genomic insulators: connecting properties to mechanism', Curr. Opin. Cell Biol., 15, pp.259-265
[38] Saitoh, N., Bell, A.C., Recillas-Targa, F., West, A.G., Simpson, M., Pikaart, M. and Felsenfeld, G. (2000): 'Structural and functional conservation at the boundaries of the chicken beta-globin domain', EMBO J., 19, pp.2315-2322
[39] Labrador, M. and Corces, V.G. (2002): 'Setting the boundaries of chromatin domains and nuclear organization', Cell, 111, pp. 151 -154
[40] Gerasimova, T.I., Byrd, K. and Corces, V.G. (2000): 'A chromatin insulator determines the nuclear localization of DNA', Mol. Cell, 6, pp.1025-1035
[41] Ishii, K., Arib, G., Lin, C., Van Houwe, G. and Laemmli, U.K. (2002): 'Chromatin boundaries in budding yeast: the nuclear pore connection', Cell, 109, pp.551-562
[42] Berezney, R., Mortillaro, M.J., Ma, H., Wei, X., and Samarabandu, J. (1995): 'The nuclear matrix: a structural milieu for genomic function', Int. Rev. Cytol., 162A, pp.1-65
[43] van Driel, R., Wansink, D.G., van Steensel, B., Grande ,M.A., Schul, W. and de Jong, L. (1995): 'Nuclear domains and the nuclear matrix', Int. Rev. Cytol., 162A, pp. 151 -189
[44] Cook, P.R. (1999): 'The organization of replication and transcription', Science, 284, pp.1790-1795
[45] Yasui, D., Miyano, M., Cai S, Varga-Weisz, P. and Kohwi-Shigematsu, T. ( 2002): 'SATB1 targets chromatin remodelling to regulate genes over long distances', Nature, 419, pp.641-645
[46] Martens, J.H., Verlaan, M., Kalkhoven, E., Dorsman, J.C. and Zantema, A. (2002): 'Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes', Mol. Cell Biol., 22, pp.2598-2606
[47] Iarovaia, O.V., Akopov, S.B., Nikolaev, L.G., Sverdlov, E.D. and Razin, S.V. (2005): 'Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix', Nucleic Acids Res., 33, pp.4157-4163
[48] Heng, H.H., Goetze, S., Ye, C.J., Liu, G., Stevens, J.B., Bremer, S.W., Wykes, S.M., Bode, J. and Krawetz, S.A. (2004): 'Chromatin loops are selectively anchored using scaffold/matrix-attachment regions', J. Cell Sci., 117, pp.999-1008
[49] Gribnau, J., Diderich, K., Pruzina, S., Calzolari, R. and Fraser, P. (2000): 'Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus', Mol. Cell, 5, pp.377-386
[50] Rogan, D.F., et al, (2004): 'Analysis of intergenic transcription in the human IL-4/IL-13 gene cluster', Proc. Natl. Acad. Sci U S A, 101, pp. 2446-2451
[51] H. Szutorisz, C. Canzonetta, A. Georgiou, C.M. Chow, L. Tora, N. Dillon, Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage, Mol. Cell. Biol, 25(2005)1804-1820.
[52] S. Schmitt, M. Prestel, R.Paro, Intergenic transcription through a polycomb group response element counteracts silencing, Genes. Dev, 19(2005) 697-708.
[53] G.Rank, M.Prestel, and R. Paro, Transcription through intergenic chromosomal memory elements of the Drosophila bithorax complex correlates with an epigenetic switch, Mol. Cell. Biol, 22(2002) 8026-8034.
[54] J.A.Martens, L. Laprade, and F.Winston, Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene, Nature, 429(2004) 571-574.
[55] V.Schramke, et al, RNA-interference-directed chromatin modification coupled to RNA polymerase II transcription, Nature, 435(2005) 1275-9.
[56] T.Sawado, J.Halow, M.A.Bender, M.Groudine, The beta -globin locus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation, Genes.Dev, 17(2003) 1009-18
[57] S.Schmitt, and R.Paro, Gene regulation: a reason for reading nonsense, Nature, 429(2004) 510-511.
[58] V.Ambros, The functions of animal microRNAs, Nature, 431(2004) 350-355.
[59] A.E. Pasquinelli, S. Hunter, J.Bracht, MicroRNAs: a developing story, Curr. Opin. Genet. Dev, 15(2005) 200-205.
[60] L. He, G.J. Hannon, MicroRNAs: small RNAs with a big role in gene regulation, Nat. Rev. Genet, 5(2004)522-531.
[61] R.Sunkar, T. Girke, J.K.Zhu, Identification and characterization of endogenous small interfering RNAs from rice, Nucleic. Acids. Res, 33(2005) 4443-4454.
[62] B.J.Reinhart, E.G.Weinstein, M.W.Rhoades, B.Bartel, and D.P.Bartel, MicroRNAs in plants, Genes. Dev, 16(2002) 1616-1626.
[63] M.Lagos-Quintana, R. Rauhut, J. Meyer, A. Borkhardt, and T.Tuschl, New microRNAs from mouse and human, Rna, 9(2003) 175-179.
[64] S.Yekta, I.H.Shih, and D.P. Bartel, MicroRNA-directed cleavage of HOXB8 mRNA, Science, 304(2004) 594-596.
[65] W.W.Gibbs, The unseen genome: gems among the junk, Sci. Am, 289 (2003) 26-33.
[66] J.E.Barrick, et al, New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control, Proc. Natl. Acad. Sci U S A, 101(2004) 6421-6426.
[67] K.A.Corbino, Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria, Genome. Biol, 6(2005) R70.
[68] F.Haddad, P.W. Bodell, A.X. Qin, J.M.Giger, and K.M.Baldwin, Role of antisense RNA in coordinating cardiac myosin heavy chain gene switching, J.Biol.Chem, 278(2003) 37132-37138.
[69] J.L.Rinn, et al, The transcriptional activity of human Chromosome 22, Genes. Dev, 17 (2003) 529-540.
[70] Pennacchio LA, Rubin EM. Genomic strategies to identify mammalian regulatory sequences. Nat Rev Genet. 2001 Feb;2(2): 100-9.
[71] Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, Zeitlinger J, Jennings EG, Murray HL, Gordon DB, Ren B, Wyrick JJ, Tagne JB, Volkert TL, Fraenkel E, Gifford DK, Young RA. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science. 2002 Oct 25;298(5594):799-804.
[72] Harismendy O, Gendrel CG, Soularue P, Gidrol X, Sentenac A, Werner M, Lefebvre O. Genome-wide location of yeast RNA polymerase III transcription machinery. EMBO J. 2003 Sep 15;22(18):4738-47.
[73] Martone R, Euskirchen G, Bertone P, Hartman S, Royce TE, Luscombe NM, Rinn JL, Nelson FK, Miller P, Gerstein M, Weissman S, Snyder M. Distribution of NF-kappaB-binding sites across human chromosome 22. Proc Natl Acad Sci U S A. 2003 Oct 14; 100(21): 12247-52.
[74] Wei GH, Liu DP, Liang CC. Charting gene regulatory networks: strategies, challenges and perspectives. Biochem J. 2004 Jul 1;381(Pt 1):1-12.
[75] Hardison RC. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet. 2000 Sep;16(9):369-72.
[76] Gottgens B, Barton LM, Gilbert JG, Bench AJ, Sanchez MJ, Bahn S, Mistry S, Grafham D, McMurray A, Vaudin M, Amaya E, Bentley DR, Green AR, Sinclair AM. Analysis of vertebrate SCL loci identifies conserved enhancers. Nat Biotechnol. 2000 Feb; 18(2): 181-6.
[77] Hood L, Rowen L, Koop BF. Human and mouse T-cell receptor loci: genomics, evolution, diversity, and serendipity. Ann N Y Acad Sci. 1995 Jun 30;758:390-412.
[78] Koop BF, Hood L.Striking sequence similarity over almost 100 kilobases of human and mouse T-cell receptor DNA. Nat Genet. 1994 May;7(1):48-53.
[79] Hardison R, Krane D, Vandenbergh D, Cheng JF, Mansberger J, Taddie J, Schwartz S, Huang XQ, Miller W. Sequence and comparative analysis of the rabbit alpha-like globin gene cluster reveals a rapid mode of evolution in a G + C-rich region of mammalian genomes. J Mol Biol. 1991 Nov 20;222(2):233-49.
[80] Lockhart DJ, Winzeler EA. Genomics, gene expression and DNA arrays. Nature. 2000 Jun 15;405(6788):827-36.
[81] Hughes JD, Estep PW, Tavazoie S, Church GM. Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae. J Mol Biol. 2000 Mar 10;296(5): 1205-14.
[82] Greenfield A. Applications of DNA microarrays to the transcriptional analysis of mammalian genomes. Mamm Genome. 2000 Aug;11(8):609-13.
[83] Hill AA, Hunter CP, Tsung BT, Tucker-Kellogg G, Brown EL. Genomic analysis of gene expression in C. elegans. Science. 2000 Oct 27;290(5492):809-12.
[84] Prestridge DS. Computer software for eukaryotic promoter analysis. Methods Mol Biol. 2000; 130:265-95
[85] Perier RC, Praz V, Junier T, Bonnard C, Bucher P. The eukaryotic promoter database (EPD). Nucleic Acids Res. 2000 Jan l;28(1):302-3.
[86] Wingender E, Chen X, Hehl R, Karas H, Liebich I, Matys V, Meinhardt T, Pruss M, Reuter I, Schacherer F. TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res. 2000 Jan l;28(1):316-9.
[87] Albert,R & Barabasi,A.-L. statistical mechanics of complex networks, Rev Mod. Phys, 74,47-972002.
[88] Dorogovtsev,S.N.&Mendes, J.F.F. Evolution of networks:from biological nets to the internet and www(Oxford University Press, Oxford,2003)
[89] Bomhoudt,S&Schuster,H.G. Handbook of graphs and networks: from the genome to the internet(Wiley-VCH, Berlin, Germany,2003)
[90] Strogatz SH. Exploring complex networks. Nature. 2001 Mar 8;410(6825):268-76.
[91] Barabasi AL, Oltvai ZN. Network biology: understanding the cell's functional organization. Nat Rev Genet. 2004 Feb;5(2): 101-13.
[92] Albert R, Jeong H, Barabasi AL. Error and attack tolerance of complex networks Nature. 2000 Jul 27;406(6794):378-82.
[93] Dezso Z, Oltvai ZN, Barabasi AL. Bioinformatics analysis of experimentally determined protein complexes in the yeast Saccharomyces cerevisiae. Genome Res. 2003 Nov;13(11):2450-4.
[94] Barkai N, Leibler S. Robustness in simple biochemical networks. Nature. 1997 Jun 26;387(6636):913-7.
[95] Alon U, Surette MG, Barkai N, Leibler S. Robustness in bacterial chemotaxis. Nature. 1999 Jan 14;397(6715): 168-71.
[96] Wray G. A., Hahn M. W., Abouheif E., Balhoff J. P., Pizer M., Rockman M. V. et al. (2003) The evolution of transcriptional regulation in eukaryotes. Mol. Biol. Evol. 20: 1377-1419
[97] Stamatoyannopoulos J. A. (2004) The genomics of gene expression. Genomics 84: 449-457
[98] Wittkopp PJ. Genomic sources of regulatory variation in cis and in trans. Cell Mol Life Sci. 2005 Aug;62(16): 1779-83.
[99] Arnone, M.I., Davidson, E.H., 1997. The hardwiring of development: organization and function of genomic regulatory systems. Development 124, 1851- 1864.
[100] Barrow, J.R., Stadler, H.S., Capecchi, M.R., 2000. Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127, 933- 944.
[101] Andrioli, L.P.M., Vasisht, V., Theodosopoulou, E., Oberstein, A., Small, S., 2002. Anterior repression of a Drosophila stripe enhancer requires three position-specific mechanisms. Development 129, 4931-4940.
[102] Gaudet, J., Mango, S.E., 2002. Regulation of organogenesis by the Caenorhabditis elegans, FoxA protein PHA-41. Science 295, 821- 825.
Ashe HL, Monks J, & Wijgerde M. Intergenic transcription and transinduction of the human beta-globin locus. Genes Dev. 11, 2494-509. (1997)
Belmont, A. Curr. Opin. Cell Biol. 15, 304 (2003).
Berezney, R. & Wei, X. The new paradigm: integrating genomic function and nuclear architecture. J. Cell. Biochem. 31, S238-S242 (1998).
Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3,207-217(1999).
Bulger, M., et al. ChIPs of the β-globin locus: unraveling gene regulation within an active domain. Curr. Opin. Genet. Dev. 12, 170-177. (2002)
Bungert J., et al. Synergistic regulation of human β-globin gene switching by locus control region elements HS3 and HS4. Genes Dev. 9: 3083-3096. (1995)
Cai, S. & Kohwi-Shigematsu, T. Intranuclear relocalization of matrix binding sites during T cell activation detected by amplified fluorescence in situ hybridization. Methods 19, 394-402 (1999).
Cai, S., Han, H.J., & Kohwi-Shigematsu, T. Tissue-specific nuclear architecture and gene expession regulated by SATB1. nature genetics. 34. 42-52,(2003).
Carter, D., et al. Long-range chromatin regulatory interactions in vivo. Nat Genet.32, 623-6. (2002)
Chambeyron, S. & Bickmore, W. A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription Genes Dev. 18, 1119 (2004).
Chen, H., R.J. Lin, W. Xie, D. Wilpitz, & R.M. Evans. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell 98: 675-686. (1999)
Chien, C.T., S. Buck, R. Sternglanz & D. Shore. Targeting of SIR1 protein establishes transcriptional silencing at HM loci and telomeres in yeast. Cell. 75, 531-541. (1993)
Cockerill,P.N. & Garrard,W.T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell, 44, 273-282.(1986)
Cremer T.&Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature, 2, 292-301(2001).
Cremer, T. et al. Chromosome territories, interchromatin domain compartment and nuclear matrix. An integrated view of the functional nuclear architecture. Crit. Rev. Eukaryotic Gene Expression 12, 179-212 (2000).
Cremer, T., Dietzel, S., Eils, R., Lichter, P. & Cremer, C. in Kew Chromosome Conference IV (ed. Benett, M. D.) 63-81 (Royal Botanic Gardens, Kew), (1995)
de Belle, I., Cai, S. & Kohwi-Shigematsu, T. The genomic sequences bound to special AT-rich sequence-binding protein 1 (SATB1) in vivo in Jurkat T cells are tightly associated with the nuclear matrix at the bases of the chromatin loops. J. Cell Biol. 141, 335-348 (1998).
Deisserroth, A., et al. Localization of the human α-globin structural gene to chromosome16 in somatic cell hybrids by molecular hybridization assay, Cell. 12: 205-218.(1977)
Desserroth, A., et al. Chromosomal localization of human β-globin gene on human chromosome 11 in somatic cell hybrids. Proc. Natl. Acad. Sci. USA. 1978, 75:1456-1460. (2001)
Dickinson, L.A., Joh, T., Kohwi, Y. & Kohwi-Shigematsu, T. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell 70, 631-645 (1992).
Evans T, Felsenfeld G & Reitman M. Control of globin gene transcription. Annual Review in Cell Biology. 6, 95-124. (1990)
Forrester, W.C., et al. A developmentally stable chromatin structure in the human β-globin gene cluster, Proc. Natl. Acad. Sci. USA. 83: 1359-1363. (1986)
Galiova, G., et al. Nuclear topography of h-like globin gene cluster in IL-3-stimulated human leukemic K-562 cells.Blood Cells, Molecules, and Diseases 33 4 - 14 (2004).
Gong, Q.H., et al.,Transcriptional role of a conserved GATA-1 site in the human ε-Globin Gene Promoter. Mol. Cell. Bio.,11, 2558-2566, (1991)
Gotta, M. & S.M. Gasser. Nuclear organization and transcriptional silencing in yeast. Experientia 52: 1136-1147.(1996)
Gribnau, J., et al. Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Mol Cell. 5, 377-86. (2000)
Grosveld, F., et al. Position-independent, high-level expression of the human β-globin gene in transgenic mice. Cell. 1987, 51: 975-985.
Grosveld, F., et al The regulation of human globin gene switching. Philos. Trans. R. Soc. Lond. Ser. B 339, 183-191. (1993)
Gruenbaum Y, Goldman RD, Meyuhas R, Mills E, Margalit A, Fridkin A, Dayani Y, Prokocimer M, Enosh A. The nuclear lamina and its functions in the nucleus. Int Rev Cytol 226, 1-62.(2003)
Gui C. & Dean A. Acetylation of a specific promoter nucleosome accompanies activation of the ε-globin gene by β-globin locus control region HS2. Mol. Cell. Bio. 21, 1155-1163.(2001)
Heng, H. H. Q. et al, Chromatin loops are selectively anchored using scaffold/matrix-attachment regions. J. of Cell Sci. 117,999-1008,(2004).
Jackson, D. Understanding nuclear organization: when information becomes knowledge. EMBO reports 6, 213-217. (2005).
Jenuwein T, & Allis CD. Translating the histone code. Science. 293. 1074-80. (2001)
Karlsson S & Nienhuis A. Developmental regulation of human globin genes, Annual Review in Biochemistry 54. 1071-1108. (1985)
Kosak, S. T.& Groudine, M. Gene order and dynamic domains. Science, 22, 644-647 (2004).
Larovaia, O. V. et al Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix. Nucleic Acids Research, 33, 4157-4163 (2005)
Li Q., Harju S. & Peterson K.R. Locus control regions: coming of an age at a decade plus Trends Genet. 15. 403-408(1999)
Litt, M.D., et al. Correlation between histone lysine methylation and developmental changes at the chicken β-globin locus. Science a 293. 2453-2455. (2001)
Litt, M.D., et al. Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci. EMBO J. b 20. 2224-2235.(2001)
Maillet, L., C. Boscheron, M. Gotta, S. Marcand, E. Gilson, and S.M. Gasser. Evidence for silencing compartments within the yeast nucleus: A role for telomere proximity and Sir protein concentration in silencer-mediated repression. Genes & Dev. 10: 1796-1811. (1996).
Matera, A. G. Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol. 9, 302-309 (1999).
Milot, E., et al. Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription. Cell 87, 105-114.(1996)
Misteli, T. Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function. J. Cell Sci. 113, 1841-1849 (2000).
Mounkes LC, Stewart CL Aging and nuclear organization: lamins and progeria. Curr Opin Cell Biol 16: 322-327.(2004)
Munkel, C. et al. Compartmentalization of interphase chromosomes observed in simulation and experiment. J. Mol. Biol. 285, 1053-1065 (1999).
Nickerson, J. A. Experimental observations of a nuclear matrix. J. Cell Sci. 114, 463-474 (2001).
Noma K, Allis CD, & Grewal SI. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science. 293.5532.(2001)
O'Neill, L.P. and B.M. Turner. Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner. EMBO J. 14: 3946-3957.( 1995).
Parekh, B.S. and T. Maniatis. Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFNbeta promoter. Mol. Cell 3: 125-129. (1999).
Pikaart M.J., Recillas-Targa F., & Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators. Genes Dev. 12: 2852-2862. (1998)
Pitot, H. C. et al. A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors. Clin. Cancer Res. 8, 712-717 (2002).
Ragoczy, T., et al. A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements. Chromosome Research, 11, 513-525, (2003).
Raich, N., et al. GATAI and YY1 are developmental repressors of the human s-globin gene. The EMBO J. 14, 801-809, (1995)
Schubeler D, et al, Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human b-globin locus. Genes & Dev. 14, 940-950, (2000).
Schubeler D., Francastel C, Cimbora D.M., et al. Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human 3 -globin locus. Genes Dev 14: 940-950. (2000)
Schwartz, G. H. et al. A phase I study of bizelesin, a highly potent and selective DNA-interactive agent, in patients with advanced solid malignancies. Ann. Oncol. 14, 775-782 (2003).
Seo, J., Lozano, M.M. & Dudley, J. P. Nuclear matrix binding regulates SATB1-mediated transcriptional repression. J. of Bio. Chem. 280, 24600-24609, (2005).
Sun ZW, & Allis CD. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature. 418(6893): 104-8. (2002)
Townes, T.M. & Behringer R.R. Human globin locus activation region (LAR): role in temporal control. Trends Genet. 6, 219-223. (1990)
Tuan D, Solomon W, Li Q, et al. The "β-like globin " gene domain in human erythroid cells, Proc. Natl. Acad. Sci. USA. 82: 6384-6388.(1985)
Visser, A. E., Jaunin, F., Fakan, S. & Aten, J. A. High resolution analysis of interphase chromosome domains. J. Cell Sci. 113, 2585-2593 (2000).
Volpi, E. V. et al., J. Cell Sci. 113, 1565 (2000).
Wang, J. et al., J. Cell Biol. 164, 515 (2004).
Wijgerde N., Grosveld F., & Fraser P. Transcription complex stability and chromatin dynamics in vivo. Nature. 377. 209-213 (1995)
Wilson C.J., Chao D.M., Imbalzano A.N., et al. RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling, Cell, 84: 235-244, (1996) .
Wittschieben B.O., Otero G., Bizemont T.D., Fellows J., et al. A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme, Mol. Cell, 1: 123-128. (1999)
Woynarowski, J. M. AT islands- their nature and potential for anticancer strategies. Curr. Cancer Drug Targets 4,219-234 (2004).
Yasui, D., et al SATB1 targets chromatin remodelling to regulate genes over long distances. Nature, 419 641-645,(2002).
Yeh, T.Y., Chuang, J.Z.& Sung, Ch.H. Dynein light chain rp3 acts as a nuclear matrixassociated transcriptional modulator in a dyneinindependent pathway. J. of Cell Sci. 118,3431-3443,(2005).
Zink, D., Fischer, A.H.& Nickerson, J. A. Nuclear structure in cancer cells.Nature reviews, 4, 677-687,(2004)
[1] Levine, M. and Tjian, R. (2003): 'Transcription regulation and animal diversity.', Nature, 424, pp. 147-51
[2] Desset, S. and Vaury, Ch. (2005): 'Transcriptional interference mediated by retrotransposons within the genome of their host: lessons from alleles of the white gene from Drosophila melanogaster', Cytogenetic and Genome Research, 110, pp. 209-214
[3] Howard, M.L.and Davidson, E.H. (2004): 'cis-Regulatory control circuits in development', Dev Biol. 271, pp. 109-118
[4] Lander,E.S. et al , (2001) : 'Initial sequencing and analysis of the human genome', Nature. 409, pp. 860-921
[5] Graveley, B.R. (2001): 'Alternative splicing: increasing diversity in the proteomic world', Trends. Genet. 17, pp. 100-107
[6] Baltimore, D. (2001): 'Our genome unveiled', Nature, 409, pp.814-6
[7] Ruvkun,G. and Hobert,O. (1998): 'The taxonomy of developmental control in Caenorhabditis elegans', Science, 282, pp.2033-2041
[8] Aoyagi, N. and Wassarman, D.A. (2000): 'Genes encoding Drosophila melanogaster RNA polymerase II general transcription factors: diversity in TFIIA and TFIID components contributes to gene-specific transcriptional regulation', J. Cell Biol. .150, pp.F45-50
[9] Wyrick, J.J.and Young, R.A. (2002): 'Deciphering gene expression regulatory networks', Curr. Opin. Genet. Dev., 12, pp. 130-136
[10] Okada, N. and Takeda, J. (2004): 'Biological significance in transposon-mediated mutation and molecular evolution-special reference to the junk DNA', Tanpakushitsu Kakusan Koso., 49, pp. 2075-2079
[11] Bowen, N.J. and Jordan, I.K. (2002): ' Transposable elements and the evolution of eukaryotic complexity', Curr. Issues Mol. Biol., 4, pp.65-76
[12] Conte, C., Dastugue, B. and Vaury, C. (2002): 'Coupling of enhancer and insulator properties identified in two retrotransposons modulates their mutagenic impact on nearby genes', Mol. Cell Biol., 22, pp. 1767-1777
[13] Miller, W.J., McDonald, J.F., Nouaud, D. and Anxolabehere, D. (1999): 'Molecular domestication - more than a sporadic episode in evolution', Genetica, 107, pp.197-207
[14] Desset, S. and Vaury, Ch., (2005): 'Transcriptional interference mediated by retrotransposons within the genome of their host: lessons from alleles of the white gene from Drosophila melanogaster', Cytogenetic and Genome Research, 110, pp.209-214
[15] Iglesias, A.R., Kindlund, E., Tammi, M. and Wadelius, C. (2004): 'Some microsatellites may act as novel polymorphic cis-regulatory elements through transcription factor binding', Gene, 341, pp.149-165
[16] Lopez, R.A., Schoetz, S. DeAngelis, K., 'Neill, D.O. and Bank, A. (2002): 'Multiple hematopoietic defects and delayed globin switching in Ikaros null mice', Proc. Natl. Acad. Sci U S A, 99, pp.602-607
[17] Pastinen, T. and Hudson, T.J. (2004): 'Cis-acting regulatory variation in the human genome', Scienc,.306, pp.647-650
[18] Weber, J.L. and Wong, C. (1993): 'Mutation of human short tandem repeats', Hum. Mol. Genet., 2, pp.1123-1128
[19] Pastinen, T. et al (2004): 'A survey of genetic and epigenetic variation affecting human gene expression', Physiol. Genomics, 16, pp. 184-193
[20] Knight, J.C., Keating, B.J., Rockett, K.A. and Kwiatkowski, D.P. (2003): 'In vivo characterization of regulatory polymorphisms by allele-specific quantification of RNA polymerase loading', Nat. Genet., 33, pp.469-475
[21] Knight, J.C., Keating, B.J. and Kwiatkowski, D.P. (2004): 'Allele-specific repression of lymphotoxin-alpha by activated B cell factor-1', Nat. Genet., 36, pp.394-399
[22] Hudson, T.J. (2003): 'Wanted: regulatory SNPs', Nat. Genet., 33, pp.439-440
[23] Takada, S. et al (2002): 'Epigenetic analysis of the Dlkl-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19', Hum. Mol. Genet, 11, pp.77-86
[24] Ferguson-Smith, A.C. (2000): 'Genetic imprinting: silencing elements have their say', Curr. Biol., 10, pp. R872-875
[25] Fedoriw, A.M., Stein, P., Svoboda, P. Schultz, R.M. and Bartolomei, M.S. (2004): 'Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting', Science, 303, pp.238-240
[26] Guo, L., Hu-Li, J. and Paul, WE. (2005): 'Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13', Immunity, 23, pp.89-99
[27] Avner, P. and Heard, E. (2001): 'X-chromosome inactivation: counting, choice and initiation', Nat. Rev. Genet., 2, pp. 59-67
[28] Jeannie, T.L Regulation of X-chromosome counting by Tsix and Xite sequences. Science, 309,29, 768-771,2005
[29] Steven, T. K. and Groudine, M. (2004): 'Gene Order and Dynamic Domains', Science, 306, pp.644-647
[30] Kosak, S.T. and Groudine M. (2004): 'Form follows function: The genomic organization of cellular differentiation', Genes. Dev., 18, pp. 1371-1384
[31] Cheutin, T., McNairn, A.J., Jenuwein, T., Gilbert, D.M., Singh, P.B. and Misteli, T. (2003): 'Maintenance of stable heterochromatin domains by dynamic HP1 binding', Science, 299, pp.721-725
[32] Chambeyron, S. and Bickmore, W. A. (2004): 'Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription', Gene. Dev., 18, pp.1119 - 1130
[33] Kosak, S.T. and Groudine, M. (2004): 'Form follows function: the genomic organization of cellular differentiation', Gene. Dev., 18, pp.1371 - 1384
[34] Cremer, T. and Cremer, C. (2001); 'Chromosome territories, nuclear architecture and gene regulation in mammalian cells', Nat. Rev. Genet., 2, pp.292-301
[35] Schubeler, D., Francastel, C, Cimbora, D.M., Reik, A., Martin, D.I. and Groudine, M. (2000): 'Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta-globin locus', Genes Dev., 14, pp.940-95,.
[36] Ragoczy, T., Telling, A., Sawado, T., Groudine, M. and Kosak, S.T. (2003): 'A genetic analysis of chromosome territory looping: diverse roles for distal regulatory elements', Chromosome Res., 11, pp.513-525
[37] Kuhn, E.J. and Geyer, P.K. (2003): 'Genomic insulators: connecting properties to mechanism', Curr. Opin. Cell Biol., 15, pp.259-265
[38] Saitoh, N., Bell, A.C., Recillas-Targa, F., West, A.G., Simpson, M., Pikaart, M. and Felsenfeld, G. (2000): 'Structural and functional conservation at the boundaries of the chicken beta-globin domain', EMBO J., 19, pp.2315-2322
[39] Labrador, M. and Corces, V.G. (2002): 'Setting the boundaries of chromatin domains and nuclear organization', Cell, 111, pp. 151 -154
[40] Gerasimova, T.I., Byrd, K. and Corces, V.G. (2000): 'A chromatin insulator determines the nuclear localization of DNA', Mol. Cell, 6, pp.1025-1035
[41] Ishii, K., Arib, G., Lin, C., Van Houwe, G. and Laemmli, U.K. (2002): 'Chromatin boundaries in budding yeast: the nuclear pore connection', Cell, 109, pp.551-562
[42] Berezney, R., Mortillaro, M.J., Ma, H., Wei, X., and Samarabandu, J. (1995): 'The nuclear matrix: a structural milieu for genomic function', Int. Rev. Cytol., 162A, pp.1-65
[43] van Driel, R., Wansink, D.G., van Steensel, B., Grande ,M.A., Schul, W. and de Jong, L. (1995): 'Nuclear domains and the nuclear matrix', Int. Rev. Cytol., 162A, pp. 151 -189
[44] Cook, P.R. (1999): 'The organization of replication and transcription', Science, 284, pp.1790-1795
[45] Yasui, D., Miyano, M., Cai S, Varga-Weisz, P. and Kohwi-Shigematsu, T. ( 2002): 'SATB1 targets chromatin remodelling to regulate genes over long distances', Nature, 419, pp.641-645
[46] Martens, J.H., Verlaan, M., Kalkhoven, E., Dorsman, J.C. and Zantema, A. (2002): 'Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes', Mol. Cell Biol., 22, pp.2598-2606
[47] Iarovaia, O.V., Akopov, S.B., Nikolaev, L.G., Sverdlov, E.D. and Razin, S.V. (2005): 'Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix', Nucleic Acids Res., 33, pp.4157-4163
[48] Heng, H.H., Goetze, S., Ye, C.J., Liu, G., Stevens, J.B., Bremer, S.W., Wykes, S.M., Bode, J. and Krawetz, S.A. (2004): 'Chromatin loops are selectively anchored using scaffold/matrix-attachment regions', J. Cell Sci., 117, pp.999-1008
[49] Gribnau, J., Diderich, K., Pruzina, S., Calzolari, R. and Fraser, P. (2000): 'Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus', Mol. Cell, 5, pp.377-386
[50] Rogan, D.F., et al, (2004): 'Analysis of intergenic transcription in the human IL-4/IL-13 gene cluster', Proc. Natl. Acad. Sci U S A, 101, pp. 2446-2451
[51] H. Szutorisz, C. Canzonetta, A. Georgiou, C.M. Chow, L. Tora, N. Dillon, Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage, Mol. Cell. Biol, 25(2005)1804-1820.
[52] S. Schmitt, M. Prestel, R.Paro, Intergenic transcription through a polycomb group response element counteracts silencing, Genes. Dev, 19(2005) 697-708.
[53] G.Rank, M.Prestel, and R. Paro, Transcription through intergenic chromosomal memory elements of the Drosophila bithorax complex correlates with an epigenetic switch, Mol. Cell. Biol, 22(2002) 8026-8034.
[54] J.A.Martens, L. Laprade, and F.Winston, Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene, Nature, 429(2004) 571-574.
[55] V.Schramke, et al, RNA-interference-directed chromatin modification coupled to RNA polymerase II transcription, Nature, 435(2005) 1275-9.
[56] T.Sawado, J.Halow, M.A.Bender, M.Groudine, The beta -globin locus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation, Genes.Dev, 17(2003) 1009-18
[57] S.Schmitt, and R.Paro, Gene regulation: a reason for reading nonsense, Nature, 429(2004) 510-511.
[58] V.Ambros, The functions of animal microRNAs, Nature, 431(2004) 350-355.
[59] A.E. Pasquinelli, S. Hunter, J.Bracht, MicroRNAs: a developing story, Curr. Opin. Genet. Dev, 15(2005) 200-205.
[60] L. He, G.J. Hannon, MicroRNAs: small RNAs with a big role in gene regulation, Nat. Rev. Genet, 5(2004)522-531.
[61] R.Sunkar, T. Girke, J.K.Zhu, Identification and characterization of endogenous small interfering RNAs from rice, Nucleic. Acids. Res, 33(2005) 4443-4454.
[62] B.J.Reinhart, E.G.Weinstein, M.W.Rhoades, B.Bartel, and D.P.Bartel, MicroRNAs in plants, Genes. Dev, 16(2002) 1616-1626.
[63] M.Lagos-Quintana, R. Rauhut, J. Meyer, A. Borkhardt, and T.Tuschl, New microRNAs from mouse and human, Rna, 9(2003) 175-179.
[64] S.Yekta, I.H.Shih, and D.P. Bartel, MicroRNA-directed cleavage of HOXB8 mRNA, Science, 304(2004) 594-596.
[65] W.W.Gibbs, The unseen genome: gems among the junk, Sci. Am, 289 (2003) 26-33.
[66] J.E.Barrick, et al, New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control, Proc. Natl. Acad. Sci U S A, 101(2004) 6421-6426.
[67] K.A.Corbino, Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria, Genome. Biol, 6(2005) R70.
[68] F.Haddad, P.W. Bodell, A.X. Qin, J.M.Giger, and K.M.Baldwin, Role of antisense RNA in coordinating cardiac myosin heavy chain gene switching, J.Biol.Chem, 278(2003) 37132-37138.
[69] J.L.Rinn, et al, The transcriptional activity of human Chromosome 22, Genes. Dev, 17 (2003) 529-540.
[70] Pennacchio LA, Rubin EM. Genomic strategies to identify mammalian regulatory sequences. Nat Rev Genet. 2001 Feb;2(2): 100-9.
[71] Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, Zeitlinger J, Jennings EG, Murray HL, Gordon DB, Ren B, Wyrick JJ, Tagne JB, Volkert TL, Fraenkel E, Gifford DK, Young RA. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science. 2002 Oct 25;298(5594):799-804.
[72] Harismendy O, Gendrel CG, Soularue P, Gidrol X, Sentenac A, Werner M, Lefebvre O. Genome-wide location of yeast RNA polymerase III transcription machinery. EMBO J. 2003 Sep 15;22(18):4738-47.
[73] Martone R, Euskirchen G, Bertone P, Hartman S, Royce TE, Luscombe NM, Rinn JL, Nelson FK, Miller P, Gerstein M, Weissman S, Snyder M. Distribution of NF-kappaB-binding sites across human chromosome 22. Proc Natl Acad Sci U S A. 2003 Oct 14; 100(21): 12247-52.
[74] Wei GH, Liu DP, Liang CC. Charting gene regulatory networks: strategies, challenges and perspectives. Biochem J. 2004 Jul 1;381(Pt 1):1-12.
[75] Hardison RC. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet. 2000 Sep;16(9):369-72.
[76] Gottgens B, Barton LM, Gilbert JG, Bench AJ, Sanchez MJ, Bahn S, Mistry S, Grafham D, McMurray A, Vaudin M, Amaya E, Bentley DR, Green AR, Sinclair AM. Analysis of vertebrate SCL loci identifies conserved enhancers. Nat Biotechnol. 2000 Feb; 18(2): 181-6.
[77] Hood L, Rowen L, Koop BF. Human and mouse T-cell receptor loci: genomics, evolution, diversity, and serendipity. Ann N Y Acad Sci. 1995 Jun 30;758:390-412.
[78] Koop BF, Hood L.Striking sequence similarity over almost 100 kilobases of human and mouse T-cell receptor DNA. Nat Genet. 1994 May;7(1):48-53.
[79] Hardison R, Krane D, Vandenbergh D, Cheng JF, Mansberger J, Taddie J, Schwartz S, Huang XQ, Miller W. Sequence and comparative analysis of the rabbit alpha-like globin gene cluster reveals a rapid mode of evolution in a G + C-rich region of mammalian genomes. J Mol Biol. 1991 Nov 20;222(2):233-49.
[80] Lockhart DJ, Winzeler EA. Genomics, gene expression and DNA arrays. Nature. 2000 Jun 15;405(6788):827-36.
[81] Hughes JD, Estep PW, Tavazoie S, Church GM. Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae. J Mol Biol. 2000 Mar 10;296(5): 1205-14.
[82] Greenfield A. Applications of DNA microarrays to the transcriptional analysis of mammalian genomes. Mamm Genome. 2000 Aug;11(8):609-13.
[83] Hill AA, Hunter CP, Tsung BT, Tucker-Kellogg G, Brown EL. Genomic analysis of gene expression in C. elegans. Science. 2000 Oct 27;290(5492):809-12.
[84] Prestridge DS. Computer software for eukaryotic promoter analysis. Methods Mol Biol. 2000; 130:265-95
[85] Perier RC, Praz V, Junier T, Bonnard C, Bucher P. The eukaryotic promoter database (EPD). Nucleic Acids Res. 2000 Jan l;28(1):302-3.
[86] Wingender E, Chen X, Hehl R, Karas H, Liebich I, Matys V, Meinhardt T, Pruss M, Reuter I, Schacherer F. TRANSFAC: an integrated system for gene expression regulation. Nucleic Acids Res. 2000 Jan l;28(1):316-9.
[87] Albert,R & Barabasi,A.-L. statistical mechanics of complex networks, Rev Mod. Phys, 74,47-972002.
[88] Dorogovtsev,S.N.&Mendes, J.F.F. Evolution of networks:from biological nets to the internet and www(Oxford University Press, Oxford,2003)
[89] Bomhoudt,S&Schuster,H.G. Handbook of graphs and networks: from the genome to the internet(Wiley-VCH, Berlin, Germany,2003)
[90] Strogatz SH. Exploring complex networks. Nature. 2001 Mar 8;410(6825):268-76.
[91] Barabasi AL, Oltvai ZN. Network biology: understanding the cell's functional organization. Nat Rev Genet. 2004 Feb;5(2): 101-13.
[92] Albert R, Jeong H, Barabasi AL. Error and attack tolerance of complex networks Nature. 2000 Jul 27;406(6794):378-82.
[93] Dezso Z, Oltvai ZN, Barabasi AL. Bioinformatics analysis of experimentally determined protein complexes in the yeast Saccharomyces cerevisiae. Genome Res. 2003 Nov;13(11):2450-4.
[94] Barkai N, Leibler S. Robustness in simple biochemical networks. Nature. 1997 Jun 26;387(6636):913-7.
[95] Alon U, Surette MG, Barkai N, Leibler S. Robustness in bacterial chemotaxis. Nature. 1999 Jan 14;397(6715): 168-71.
[96] Wray G. A., Hahn M. W., Abouheif E., Balhoff J. P., Pizer M., Rockman M. V. et al. (2003) The evolution of transcriptional regulation in eukaryotes. Mol. Biol. Evol. 20: 1377-1419
[97] Stamatoyannopoulos J. A. (2004) The genomics of gene expression. Genomics 84: 449-457
[98] Wittkopp PJ. Genomic sources of regulatory variation in cis and in trans. Cell Mol Life Sci. 2005 Aug;62(16): 1779-83.
[99] Arnone, M.I., Davidson, E.H., 1997. The hardwiring of development: organization and function of genomic regulatory systems. Development 124, 1851- 1864.
[100] Barrow, J.R., Stadler, H.S., Capecchi, M.R., 2000. Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development 127, 933- 944.
[101] Andrioli, L.P.M., Vasisht, V., Theodosopoulou, E., Oberstein, A., Small, S., 2002. Anterior repression of a Drosophila stripe enhancer requires three position-specific mechanisms. Development 129, 4931-4940.
[102] Gaudet, J., Mango, S.E., 2002. Regulation of organogenesis by the Caenorhabditis elegans, FoxA protein PHA-41. Science 295, 821- 825.