@article{542ca988d6f94245bda98821daebe17b,
title = "Bivalent-histone-marked immediate-early gene regulation is vital for VEGF-responsive angiogenesis",
abstract = "Endothelial cells (ECs) are phenotypically heterogeneous, mainly due to their dynamic response to the tissue microenvironment. Vascular endothelial cell growth factor (VEGF), the best-known angiogenic factor, activates calcium-nuclear factor of activated T cells (NFAT) signaling following acute angiogenic gene transcription. Here, we evaluate the global mapping of VEGF-mediated dynamic transcriptional events, focusing on major histone-code profiles using chromatin immunoprecipitation sequencing (ChIP-seq). Remarkably, the gene loci of immediate-early angiogenic transcription factors (TFs) exclusively acquire bivalent H3K4me3-H3K27me3 double-positive histone marks after the VEGF stimulus. Moreover, NFAT-associated Pax transactivation domain-interacting protein (PTIP) directs bivalently marked TF genes transcription through a limited polymerase II running. The non-canonical polycomb1 variant PRC1.3 specifically binds to and allows the transactivation of PRC2-enriched bivalent angiogenic TFs until conventional PRC1-mediated gene silencing is achieved. Knockdown of these genes abrogates post-natal aberrant neovessel formation via the selective inhibition of indispensable bivalent angiogenic TF gene transcription. Collectively, the reported dynamic histone mark landscape may uncover the importance of immediate-early genes and the development of advanced anti-angiogenic strategies.",
keywords = "ChIP-seq, NFAT, transcription, PTIP, VEGF, angiogenesis, bivalent histone marks, endothelial cells, immediate-early genes, noncanonical polycomb",
author = "Yasuharu Kanki and Masashi Muramatsu and Yuri Miyamura and Kenta Kikuchi and Yoshiki Higashijima and Ryo Nakaki and Suehiro, {Jun ichi} and Yuji Sasaki and Yoshiaki Kubota and Haruhiko Koseki and Hiroshi Morioka and Tatsuhiko Kodama and Mitsuyoshi Nakao and Daisuke Kurotaki and Hiroyuki Aburatani and Takashi Minami",
note = "Funding Information: We are grateful to Prof. Hiroshi Kimura (Tokyo Institute of Technology, Japan) for kindly providing phospho-CTD-specific RNAP antibodies. We appreciate T.M.{\textquoteright}s lab members for the technical assistance. We thank Editage.com for English proofreading. This work was supported by Japan Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research, JP26290035 , JP20H03432 , and JP21H02917 (to Y.K. and T.M.). Funding Information: We are grateful to Prof. Hiroshi Kimura (Tokyo Institute of Technology, Japan) for kindly providing phospho-CTD-specific RNAP antibodies. We appreciate T.M.?s lab members for the technical assistance. We thank Editage.com for English proofreading. This work was supported by Japan Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research, JP26290035, JP20H03432, and JP21H02917 (to Y.K. and T.M.). Conceptualization, Y.K. T.K. and T.M.; methodology, Y.K. M.M. Y.S. and R.N.; investigation, Y.K. M.M, Y.M, J.-i.S. Y.S. and T.M.; data curation, Y.K. K.K. R.N. and D.K.; writing ? original draft, Y.K. and T.M.; writing ? review & editing, H.A. and T.M.; funding acquisition, Y.K. H.A. and T.M.; resources, Y.K. D.K. and H.K.; supervision, M.N. and T.M. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = feb,
day = "8",
doi = "10.1016/j.celrep.2022.110332",
language = "English",
volume = "38",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}