组蛋白去甲基化酶UTX的研究进展  

Research Advances of Histone Demethylase UTX

作　　者：刘冲 黄依雪 黄昆[2] 袁杨棉 周依豪 郑凌[1] LIU Chong;HUANG Yixue;HUANG Kun;YUAN Yangmian;ZHOU Yihao;ZHENG Ling(College of Life Sciences,Wiuhan University,Wuhan 430072,China;Tongji School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wichan 430030,China)

机构地区：[1]武汉大学生命科学学院,武汉430072 [2]华中科技大学同济医学院药学院,武汉430030

出　　处：《中国细胞生物学学报》2020年第8期1387-1394,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:31871381、31671195)资助的课题。

摘　　要：UTX是一种含有多个TPR结构域和一个JmjC催化结构域的组蛋白修饰酶,主要负责去除H3K27位点的二/三甲基化。在分子机制上,UTX一方面可通过其去甲基化酶活性降低靶基因启动子或增强子上的H3K27me2/3水平,另一方面可与MLL3/4形成复合物调控增强子的H3K4甲基化水平,从而促进基因转录。此外,UTX还可以通过与组蛋白乙酰转移酶p300或去乙酰化酶HDAC1相互作用从而调控组蛋白乙酰化水平,进而影响基因转录。在生理病理方面,UTX主要参与生长发育、组织分化、免疫以及代谢等生理过程,并调控多种疾病如歌舞伎综合征、癌症等疾病的发生发展。该文对UTX的最新研究成果进行总结,并就其在疾病治疗中的可能作用展开讨论。UTX is a histone demethylase containing TPR (tetratricopeptide repeat) domains and a JmjC catalytic domain,which is responsible for the removal of di-and tri-methyl groups from H3K27 (lysine 27 residue of histone H3).Mechanistically,UTX downregulates the levels of H3K27me2/3 on the promoter or enhancer of the target genes through its demethylase activity.Furthermore,UTX binds MLL3/4 to regulate the H3K4 methylation,resulting in promoted genes transcription.Additionally,UTX interacts with the HAT (histone acetyltransferase) protein p300 or HDAC1 (histone deacetyltransferase 1),and thus regulates histone acetylation and affects gene transcription.UTX is emerging as an important player in cell growth,developmental process,differentiation,immunity,and metabolism,and has been linked to human diseases such as Kabuki syndrome and cancer.This review summarizes the recent research progresses of UTX,and discusses the potential of UTX as a therapeutic target in disease treatment.

关 键 词：组蛋白去甲基化酶 UTX H3K27me2/3去甲基化 基因转录调控 生理病理调控 

分 类 号：R341[医药卫生—基础医学]