A Selective Inhibitor and Probe of the Cellular Functions of Jumonji C Domain-Containing Histone Demethylases
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- 作者：Xuelai Luo ; Yongxiang Liu ; Stefan Kubicek ; Johanna Myllyharju ; Anthony Tumber ; Stanley Ng ; Ka Hing Che ; Jessica Podoll ; Tom D. Heightman ; Udo Oppermann ; Stuart L. Schreiber ; Xiang Wang
- 刊名：Journal of the American Chemical Society
- 出版年：2011
- 出版时间：June 22, 2011
- 年：2011
- 卷：133
- 期：24
- 页码：9451-9456
- 全文大小：893K
- 年卷期：v.133,no.24(June 22, 2011)
- ISSN：1520-5126
文摘
Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.