Division of Newborn Medicine and Program in Epigenetics, Department of Medicine, Boston Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston MA, 02115, USA.
Cell Res. 2013 Mar;23(3):326-8. doi: 10.1038/cr.2012.136. Epub 2012 Sep 18.
Histone lysine demethylases are chromatin modifiers that play important roles in many pathological processes such as inflammation and cancer, making them potentially attractive drug targets. In a recent study, Kruidenier et al. provided proof of concept by identifying chemical matters that inhibit demethylation mediated by the two related histone H3 lysine 27 demethylases, KDM6A and 6B (UTX and JMJD3). The KDM6 inhibitor shows remarkable substrate selectivity and can inhibit transcription of a plethora of pro-inflammatory genes in cell culture by altering H3K27me3 level at some of the KDM6 target genes.
组蛋白赖氨酸去甲基酶是染色质修饰物，在炎症和癌症等许多病理过程中发挥重要作用，使它们成为潜在有吸引力的药物靶点。在最近的一项研究中，Kruidenier 等人通过鉴定抑制由两个相关的组蛋白 H3 赖氨酸 27 去甲基酶 KDM6A 和 6B（UTX 和 JMJD3）介导的去甲基化的化学物质，提供了概念验证。该 KDM6 抑制剂显示出显著的底物选择性，并可以通过改变一些 KDM6 靶基因的 H3K27me3 水平，在细胞培养物中抑制大量促炎基因的转录。
