A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA

Shiyan Wang, Jiahuan Chen, Sara P. Garcia, Xiaodong Liang, Fang Zhang, Pengyi Yan, Huijing Yu, Weiting Wei, Zixuan Li, Jingfang Wang, Huangying Le, Zeguang Han, Xusheng Luo, Daniel S. Day, Sean M. Stevens, Yan Zhang, Peter J. Park, Zhi Jie Liu, Kun Sun, Guo Cheng YuanWilliam T. Pu, Bing Zhang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)193-207
Number of pages15
JournalGenome Research
Volume29
Issue number2
DOIs
StatePublished - Feb 2019

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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