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, Zhijie Liu, Kun Sun, Guo Cheng Yuan & 2 others William T. Pu, Bing Zhang

Research output: Contribution to journalArticle

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 1 2019

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Epigenomics
Gene Expression
Transcription Factors
Chromatin
Histone Code
Gene Regulatory Networks
Endothelial Cells
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Wang, S., Chen, J., Garcia, S. P., Liang, X., Zhang, F., Yan, P., ... Zhang, B. (2019). A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA. Genome Research, 29(2), 193-207. https://doi.org/10.1101/gr.239053.118

A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA. / 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, Zhijie; Sun, Kun; Yuan, Guo Cheng; Pu, William T.; Zhang, Bing.

In: Genome Research, Vol. 29, No. 2, 01.02.2019, p. 193-207.

Research output: Contribution to journalArticle

Wang, S, Chen, J, Garcia, SP, Liang, X, Zhang, F, Yan, P, Yu, H, Wei, W, Li, Z, Wang, J, Le, H, Han, Z, Luo, X, Day, DS, Stevens, SM, Zhang, Y, Park, PJ, Liu, Z, Sun, K, Yuan, GC, Pu, WT & Zhang, B 2019, 'A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA', Genome Research, vol. 29, no. 2, pp. 193-207. https://doi.org/10.1101/gr.239053.118
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, Zhijie ; Sun, Kun ; Yuan, Guo Cheng ; Pu, William T. ; Zhang, Bing. / A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA. In: Genome Research. 2019 ; Vol. 29, No. 2. pp. 193-207.
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