A Selective Inhibitor and Probe of the Cellular Functions of Jumonji C Domain-Containing Histone Demethylases

作者：Luo Xuelai; Liu Yongxiang; Kubicek Stefan; Myllyharju Johanna; Tumber Anthony; Ng Stanley; Che Ka Hing; Podoll Jessica; Heightman Tom D; Oppermann Udo; Schreiber Stuart L; Wang Xiang^*

来源：Journal of the American Chemical Society, 2011, 133(24): 9451-9456.

DOI：10.1021/ja201597b

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 histone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.

• 出版日期2011-6-22