{Reference Type}: Journal Article
{Title}: Bivalent-histone-marked immediate-early gene regulation is vital for VEGF-responsive angiogenesis.
{Author}: Kanki Y;Muramatsu M;Miyamura Y;Kikuchi K;Higashijima Y;Nakaki R;Suehiro JI;Sasaki Y;Kubota Y;Koseki H;Morioka H;Kodama T;Nakao M;Kurotaki D;Aburatani H;Minami T;
{Journal}: Cell Rep
{Volume}: 38
{Issue}: 6
{Year}: 02 2022 8
暂无{DOI}: 10.1016/j.celrep.2022.110332
{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.