RT Journal
A1 Wang, Shiyan
A1 Chen, Jiahuan
A1 Garcia, Sara P.
A1 Liang, Xiaodong
A1 Zhang, Fang
A1 Yan, Pengyi
A1 Yu, Huijing
A1 Wei, Weiting
A1 Li, Zixuan
A1 Wang, Jingfang
A1 Le, Huangying
A1 Han, Zeguang
A1 Luo, Xusheng
A1 Day, Daniel S.
A1 Stevens, Sean M.
A1 Zhang, Yan
A1 Park, Peter J.
A1 Liu, Zhi-jie
A1 Sun, Kun
A1 Yuan, Guo-cheng
A1 Pu, William T.
A1 Zhang, Bing
T1 A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA
JF Genome Research 
JO Genome Research 
YR 2019 
FD February 01 
VO 29 
IS 2 
SP 193 
OP 207 
DO 10.1101/gr.239053.118 
UL http://genome.cshlp.org/content/29/2/193.abstract 
AB 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.