C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels

doi:10.1038/s41401-019-0247-3

	C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels
	Shi, Yi 1; Ma, Hong-lei 1; Zhuang, You-wen 1,2; Wang, Xiao-xi 1; Jiang, Yi 1,2; Xu, H. Eric 1,2,3
刊名	ACTA PHARMACOLOGICA SINICA
	2019-11-01
卷号	40 期号:11 页码:1457-1465
关键词	PRC2 C10ORF12 H3K27me3 histone methyltransferase epigenetic regulation histone modification
ISSN号	1671-4083
DOI	10.1038/s41401-019-0247-3
通讯作者	Shi, Yi(shiyi@simm.ac.cn) ; Jiang, Yi(yijiang@simm.ac.cn) ; Xu, H. Eric(eric.xu@simm.ac.cn)
英文摘要	The polycomb repressive complex 2 (PRC2) catalyzes the methylation of histone H3 on lysine 27 (H3K27) to generate trimethyl-H3K27 (H3K27me3) marks, thereby leading to a repressive chromatin state that inhibits gene expression. C10ORF12 was recently identified as a novel PRC2 interactor. Here, we show that C10ORF12 specifically interacts with PRC2 through its middle region (positions 619-718). C10ORF12 significantly enhances the histone methyltransferase activity of PRC2 in vitro and dramatically increases the total H3K27me3 levels in HeLa cells. C10ORF12 also antagonizes Jarid2, which is an auxiliary factor of the PRC2.2 subcomplex, to promote increased H3K27me3 levels in HeLa cells. Moreover, C10ORF12 alters the substrate preference of PRC2. These results indicate that C10ORF12 functions as a positive regulator of PRC2 and facilitates PRC2-mediated H3K27me3 modification of chromatin. These findings provide new insight into the roles of C10ORF12 in regulating the activity of the PRC2 complex.
资助项目	Strategic Priority Research Program of CAS[XDB08020303] ; National Natural Science Foundation of China[31770796] ; Outstanding Young Scientist Foundation of CAS ; Youth Innovation Promotion Association of CAS
WOS关键词	REPRESSIVE COMPLEX 2 ; GENOMIC TARGETS ; POLYCOMB ; PROTEIN ; CHROMATIN ; RECRUITMENT ; JARID2 ; DIFFERENTIATION ; BINDING ; METHYLATION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000494974700009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281958]
专题	中国科学院上海药物研究所
通讯作者	Shi, Yi; Jiang, Yi; Xu, H. Eric
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, Ctr Struct & Funct Drug Targets, CAS Key Lab Receptor Res,VARI SIMM Ctr, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA
推荐引用方式 GB/T 7714	Shi, Yi,Ma, Hong-lei,Zhuang, You-wen,et al. C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels[J]. ACTA PHARMACOLOGICA SINICA,2019,40(11):1457-1465.
APA	Shi, Yi,Ma, Hong-lei,Zhuang, You-wen,Wang, Xiao-xi,Jiang, Yi,&Xu, H. Eric.(2019).C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels.ACTA PHARMACOLOGICA SINICA,40(11),1457-1465.
MLA	Shi, Yi,et al."C10ORF12 modulates PRC2 histone methyltransferase activity and H3K27me3 levels".ACTA PHARMACOLOGICA SINICA 40.11(2019):1457-1465.