Center for Medical Genetics; Ghent University; Ghent, Belgium.
Epigenetics. 2014 May;9(5):658-68. doi: 10.4161/epi.28298. Epub 2014 Feb 21.
In 2007, the Ubiquitously Transcribed Tetratricopeptide Repeat on chromosome X (UTX) was identified as a histone demethylase that specifically targets di- and tri-methyl groups on lysine 27 of histone H3 (H3K27me2/3). Since then, UTX has been proven essential during normal development, as it is critically required for correct reprogramming, embryonic development and tissue-specific differentiation. UTX is a member of the MLL2 H3K4 methyltransferase complex and its catalytic activity has been linked to regulation of HOX and RB transcriptional networks. In addition, an H3K27me2/3 demethylase independent function for UTX was uncovered in promoting general chromatin remodeling in concert with the BRG1-containing SWI/SNF remodeling complex. Constitutional inactivation of UTX causes a specific hereditary disorder called the Kabuki syndrome, whereas somatic loss of UTX has been reported in a variety of human cancers. Here, we compile the breakthrough discoveries made from the first disclosure of UTX as a histone demethylase till the identification of disease-related UTX mutations and specific UTX inhibitors.
2007 年，普遍转录的四肽重复序列 X 染色体（UTX）被鉴定为一种组蛋白去甲基酶，它特异性地靶向组蛋白 H3 赖氨酸 27 上的二甲基和三甲基（H3K27me2/3）。从那时起，UTX 已被证明在正常发育过程中是必不可少的，因为它对于正确的重编程、胚胎发育和组织特异性分化至关重要。UTX 是 MLL2 H3K4 甲基转移酶复合物的成员，其催化活性与 HOX 和 RB 转录网络的调节有关。此外，还发现了 UTX 的一种 H3K27me2/3 去甲基酶非依赖性功能，即与含有 BRG1 的 SWI/SNF 重塑复合物一起促进一般染色质重塑。UTX 的结构失活导致一种称为歌舞伎综合征的特定遗传性疾病，而 UTX 的体细胞缺失已在多种人类癌症中报道。在这里，我们将从首次揭示 UTX 作为组蛋白去甲基酶到鉴定与疾病相关的 UTX 突变和特定 UTX 抑制剂的突破性发现进行汇编。
