Histone acetyltransferase p300 promotes MRTF-A-mediates transactivation of VE-cadherin gene in human umbilical vein endothelial cells

Gene
Xiang-Zhu ShuTong-Cun Zhang

Abstract

Vascular endothelial cadherin (VE-cadherin) is the major determinant of endothelial cell contact integrity and is required in vascular development and angiogenesis. Serum response factor (SRF) plays essential roles in postnatal retinal angiogenesis and adult neovascularization. It is unclear whether transcription of VE-cadherin is mediated by a SRF co-activator, myocardin-related transcription factor-A (MRTF-A). Here we have demonstrated that MRTF-A is a key regulatory factor to activate the transcription of VE-cadherin in human umbilical vein endothelial cells (HUVECs). siRNA-mediated knockdown of MRTF-A decreased the level of VE-cadherin in HUVECs. Vascular endothelial growth factor (VEGF) induced MRTF-A binding to the SRF-binding site (CArG box) within VE-cadherin promoter. Histone acetyltransferase p300 and MRTF-A could synergistically augment the expression of VE-cadherin by enhancing acetylation of histone3K9 (H3K9Ac), histone3K14 (H3K14Ac) and histone4 at the SRF-binding site within VE-cadherin promoter. Taken together, these data identified a detailed regulatory mechanism of VE-cadherin gene expression.

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Citations

May 30, 2015·Cellular and Molecular Life Sciences : CMLS·Joseph M Miano, Xiaochun Long
Oct 18, 2015·Biochemical and Biophysical Research Communications·Hongpeng HeTong-Cun Zhang
Dec 19, 2018·International Journal of Molecular Sciences·Paula HeppUdo Jeschke
Mar 5, 2021·Journal of Reproductive Immunology·Sarah MeisterThomas Kolben
Apr 13, 2021·Frontiers in Molecular Biosciences·Yueyuan WangJun Du
May 18, 2021·Frontiers in Cell and Developmental Biology·Zhi FangQing R Miao

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