Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.
J Am Chem Soc. 2011 Jun 22;133(24):9451-6. doi: 10.1021/ja201597b. Epub 2011 May 31.
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.
组蛋白甲基化是调控基因表达、基因组稳定性、DNA 修复和基因组印记的重要染色质标记。组蛋白去甲基化酶是最近发现的组蛋白修饰酶家族。在这里，我们报告了一种小分子 Jumonji C 结构域组蛋白去甲基化酶抑制剂的特性。该抑制剂来源于基于结构的设计，优先抑制三甲基赖氨酸去甲基酶亚家族。其甲酯前药甲基stat 在细胞中选择性抑制 Jumonji C 结构域组蛋白去甲基化酶，可能是研究染色质及其在表观遗传学中作用的有用小分子探针。
