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VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis

Author

Listed:
  • Jiahuan Chen

    (Shanghai Jiao Tong University)

  • Yi Fu

    (Shanghai Jiao Tong University)

  • Daniel S. Day

    (Harvard Medical School
    Harvard/MIT Division of Health Sciences and Technology)

  • Ye Sun

    (Harvard Medical School/Children’s Hospital Boston)

  • Shiyan Wang

    (Shanghai Jiao Tong University)

  • Xiaodong Liang

    (Shanghai Jiao Tong University)

  • Fei Gu

    (Boston Children’s Hospital)

  • Fang Zhang

    (Shanghai Jiao Tong University)

  • Sean M. Stevens

    (Boston Children’s Hospital)

  • Pingzhu Zhou

    (Boston Children’s Hospital)

  • Kai Li

    (Boston Children’s Hospital)

  • Yan Zhang

    (Shanghai Jiao Tong University
    Children’s Hospital Boston)

  • Ruei-zeng Lin

    (Children’s Hospital Boston)

  • Lois E. H. Smith

    (Harvard Medical School/Children’s Hospital Boston)

  • Jin Zhang

    (Boston Children’s Hospital)

  • Kun Sun

    (Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine)

  • Juan M. Melero-Martin

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard University)

  • Zeguang Han

    (Shanghai Jiao Tong University)

  • Peter J. Park

    (Harvard Medical School)

  • Bing Zhang

    (Shanghai Jiao Tong University
    Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine)

  • William T. Pu

    (Boston Children’s Hospital
    Harvard University)

Abstract

Release of promoter-proximally paused RNA polymerase II (RNAPII) is a recently recognized transcriptional regulatory checkpoint. The biological roles of RNAPII pause release and the mechanisms by which extracellular signals control it are incompletely understood. Here we show that VEGF stimulates RNAPII pause release by stimulating acetylation of ETS1, a master endothelial cell transcriptional regulator. In endothelial cells, ETS1 binds transcribed gene promoters and stimulates their expression by broadly increasing RNAPII pause release. 34 VEGF enhances ETS1 chromatin occupancy and increases ETS1 acetylation, enhancing its binding to BRD4, which recruits the pause release machinery and increases RNAPII pause release. Endothelial cell angiogenic responses in vitro and in vivo require ETS1-mediated transduction of VEGF signaling to release paused RNAPII. Our results define an angiogenic pathway in which VEGF enhances ETS1–BRD4 interaction to broadly promote RNAPII pause release and drive angiogenesis.

Suggested Citation

  • Jiahuan Chen & Yi Fu & Daniel S. Day & Ye Sun & Shiyan Wang & Xiaodong Liang & Fei Gu & Fang Zhang & Sean M. Stevens & Pingzhu Zhou & Kai Li & Yan Zhang & Ruei-zeng Lin & Lois E. H. Smith & Jin Zhang , 2017. "VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00405-x
    DOI: 10.1038/s41467-017-00405-x
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