Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition

doi:10.1093/nar/gkw126

	Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition
	Chang, Hongyuan 1,6; Liu, Yuwei 6; Xue, Mengzhu 6; Liu, Haiyue 1,2; Du, Shaowei 3,6; Zhang, Liwen 1,4,5,6; Wang, Peng 1,5,6
刊名	NUCLEIC ACIDS RESEARCH
	2016-04-07
卷号	44 期号:6 页码:2514-2527
ISSN号	0305-1048
DOI	10.1093/nar/gkw126
文献子类	Article
英文摘要	Epithelial-to-mesenchymal transition (EMT) is a complex multistep process in which phenotype switches are mediated by a network of transcription factors (TFs). Systematic characterization of all dynamic TFs controlling EMT state transitions, especially for the intermediate partial-EMT state, represents a highly relevant yet largely unexplored task. Here, we performed a computational analysis that integrated time-course EMT transcriptomic data with public cistromic data and identified three synergistic master TFs (ETS2, HNF4A and JUNB) that regulate the transition through the partial-EMT state. Overexpression of these regulators predicted a poor clinical outcome, and their elimination readily abolished TGF-beta-induced EMT. Importantly, these factors utilized a clique motif, physically interact and their cumulative binding generally characterized EMT-associated genes. Furthermore, analyses of H3K27ac ChIP-seq data revealed that ETS2, HNF4A and JUNB are associated with super-enhancers and the administration of BRD4 inhibitor readily abolished TGF-beta-induced EMT. These findings have implications for systematic discovery of master EMT regulators and super-enhancers as novel targets for controlling metastasis.
资助项目	National Natural Science Foundation of China (NSFC)[31271413] ; Science and Technology Commission of Shanghai Municipality[12DZ1910800] ; Chinese Academy of Sciences 'Hundred Talent Program'[00000000]
WOS关键词	TGF-BETA ; SUPER-ENHANCERS ; REGULATORY NETWORKS ; CELL-MIGRATION ; CANCER ; EXPRESSION ; PROGRESSION ; METASTASIS ; INHIBITION ; ACTIVATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000374570500014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276079]
专题	中国科学院上海药物研究所
通讯作者	Wang, Peng
作者单位	1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Biochem & Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 3.Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd,Zhangjiang High Tech Pk, Shanghai 201203, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd,Zhangjiang High Tech Pk, Shanghai 201210, Peoples R China 6.Chinese Acad Sci, Shanghai Adv Res Inst, Lab Syst Biol, 100 Haike Rd,Zhangjiang High Tech Pk, Shanghai 201210, Peoples R China;
推荐引用方式 GB/T 7714	Chang, Hongyuan,Liu, Yuwei,Xue, Mengzhu,et al. Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition[J]. NUCLEIC ACIDS RESEARCH,2016,44(6):2514-2527.
APA	Chang, Hongyuan.,Liu, Yuwei.,Xue, Mengzhu.,Liu, Haiyue.,Du, Shaowei.,...&Wang, Peng.(2016).Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition.NUCLEIC ACIDS RESEARCH,44(6),2514-2527.
MLA	Chang, Hongyuan,et al."Synergistic action of master transcription factors controls epithelial-to-mesenchymal transition".NUCLEIC ACIDS RESEARCH 44.6(2016):2514-2527.