Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis

Research output: Contribution to journalArticle


  • Jiahuan Chen
  • Xiaodong Liang
  • Shasha Zhang
  • Shiyan Wang
  • Sara P. Garcia
  • Pengyi Yan
  • Huijing Yu
  • Zixuan Li
  • Li Liu
  • Fang Zhang
  • Weiting Wei
  • Huangying Le
  • Yan Zhang
  • Guo cheng Yuan
  • Sun Chen
  • Yingwei Chen
  • Kun Sun
  • William T. Pu
  • Bing Zhang

External Institution(s)

  • Shanghai Jiao Tong University
  • Huaiyin Institute of Technology
  • Harvard University


Original languageEnglish (US)
Article number75
JournalCell Death and Disease
Issue number1
StatusPublished - Jan 1 2020


The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA (vascular endothelial growth factor A) stimulation, we discovered that BDs are widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The BDs responsive to VEGFA have more permissive chromatin environment comparing to other BDs. The initial activation of bivalent genes depends on RNAPII pausing release induced by EZH1 rather than removal of H3K27me3. The later suppression of bivalent gene expression depended on KDM5A recruitment by its interaction with PRC2. Importantly, EZH1 promoted both in vitro and in vivo angiogenesis by upregulating EGR3, whereas KDM5A dampened angiogenesis. Collectively, this study demonstrates a novel dual function of BDs in endothelial cells to control VEGF responsiveness and angiogenesis.

Citation formats


Chen, J., Liang, X., Zhang, S., Wang, S., Garcia, S. P., Yan, P., ... Zhang, B. (2020). Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis. Cell Death and Disease, 11(1), [75].


Chen, J, Liang, X, Zhang, S, Wang, S, Garcia, SP, Yan, P, Yu, H, Li, Z, Liu, L, Zhang, F, Wei, W, Le, H, Zhang, Y, Yuan, GC, Chen, S, Chen, Y, Sun, K, Pu, WT & Zhang, B 2020, 'Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis', Cell Death and Disease, vol. 11, no. 1, 75.