Author:
Wang Shiyan,Chen Jiahuan,Garcia Sara P.,Liang Xiaodong,Zhang Fang,Yan Pengyi,Yu Huijing,Wei Weiting,Li Zixuan,Wang Jingfang,Le Huangying,Han Zeguang,Luo Xusheng,Day Daniel S.,Stevens Sean M.,Zhang Yan,Park Peter J.,Liu Zhi-jie,Sun Kun,Yuan Guo-cheng,Pu William T.,Zhang Bing
Abstract
Cell behaviors are dictated by epigenetic and transcriptional programs. Little is known about how extracellular stimuli modulate these programs to reshape gene expression and control cell behavioral responses. Here, we interrogated the epigenetic and transcriptional response of endothelial cells to VEGFA treatment and found rapid chromatin changes that mediate broad transcriptomic alterations. VEGFA-responsive genes were associated with active promoters, but changes in promoter histone marks were not tightly linked to gene expression changes. VEGFA altered transcription factor occupancy and the distal epigenetic landscape, which profoundly contributed to VEGFA-dependent changes in gene expression. Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network, which revealed that the small MAF transcription factors are master regulators of the VEGFA transcriptional program and angiogenesis. Collectively these results revealed that extracellular stimuli rapidly reconfigure the chromatin landscape to coordinately regulate biological responses.
Funder
National Institutes of Health
American Heart Association
NIH
Boston Children's Hospital Department of Cardiology
National Natural Science Foundation of China
Thousand Young Talent Award
Shanghai Municipal Education Commission
Ministry of Science and Technology
National Key Research and Development Program of China
AHA Scientist Development
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics (clinical),Genetics
Cited by
11 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献