BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos

	BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos
	Liu, W; Stein, P; Cheng, X; Yang, W; Shao, NY; Morrisey, EE; Schultz, RM; You, J
刊名	CELL DEATH AND DIFFERENTIATION
	2014
卷号	21 期号:12 页码:1950-1960
通讯作者	You, J (reprint author), Univ Penn, Perelman Sch Med, Dept Microbiol, 3610 Hamilton Walk,201C Johnson Pavil, Philadelphia, PA 19104 USA.,jianyou@mail.med.upenn.edu
英文摘要	Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader implicated in the pathogenesis of a number of different cancers and other diseases. Brd4-null mouse embryos die shortly after implantation and are compromised in their ability to maintain the inner cell mass, which gives rise to embryonic stem cells (ESCs). Here we report that BRD4 regulates expression of the pluripotency factor Nanog in mouse ESCs and preimplantation embryos, as well as in human ESCs and embryonic cancer stem cells. Inhibition of BRD4 function using a chemical inhibitor, small interfering RNAs, or a dominant-negative approach suppresses Nanog expression, and abolishes the self-renewal ability of ESCs. We also find that BRD4 associates with BRG1 (brahma-related gene 1, aka Smarca4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4)), a key regulator of ESC self-renewal and pluripotency, in the Nanog regulatory regions to regulate Nanog expression. Our study identifies Nanog as a novel BRD4 target gene, providing new insights for the biological function of BRD4 in stem cells and mouse embryos. Knowledge gained from these non-cancerous systems will facilitate future investigations of how Brd4 dysfunction leads to cancers.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	SELF-RENEWAL ; GENE-EXPRESSION ; SUPER-ENHANCERS ; GROUND-STATE ; PROTEIN BRD4 ; TRANSCRIPTIONAL REGULATION ; SELECTIVE-INHIBITION ; ACETYLATED CHROMATIN ; MITOTIC CHROMOSOMES ; BROMODOMAIN PROTEIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000345016100011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/251]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Liu, W,Stein, P,Cheng, X,et al. BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos[J]. CELL DEATH AND DIFFERENTIATION,2014,21(12):1950-1960.
APA	Liu, W.,Stein, P.,Cheng, X.,Yang, W.,Shao, NY.,...&You, J.(2014).BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos.CELL DEATH AND DIFFERENTIATION,21(12),1950-1960.
MLA	Liu, W,et al."BRD4 regulates Nanog expression in mouse embryonic stem cells and preimplantation embryos".CELL DEATH AND DIFFERENTIATION 21.12(2014):1950-1960.