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

Xiang-Zhu Shu; Li-Nan Zhang; Rui Zhang; Cai-Jiao Zhang; Hong-Peng He; Hao Zhou; Nan Wang; Tong-Cun Zhang

doi:10.1016/j.gene.2015.02.076

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

Gene. 2015 May 25;563(1):17-23. doi: 10.1016/j.gene.2015.02.076. Epub 2015 Mar 5.

Authors

Xiang-Zhu Shu¹, Li-Nan Zhang¹, Rui Zhang¹, Cai-Jiao Zhang¹, Hong-Peng He¹, Hao Zhou¹, Nan Wang², Tong-Cun Zhang³

Affiliations

¹ Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
² Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China. Electronic address: wn929@tust.edu.cn.
³ Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China; Institute of Biology and Medicine, Wuhan University of Science and Technology, 430000, PR China. Electronic address: tony@tust.edu.cn.

PMID: 25746323
DOI: 10.1016/j.gene.2015.02.076

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.

Keywords: MRTF-A; Transcription regulation; VE-cadherin; p300.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Antigens, CD / genetics*
Antigens, CD / metabolism
Binding Sites
Cadherins / genetics*
Cadherins / metabolism
Gene Expression Regulation
Gene Knockdown Techniques
Histones / metabolism
Human Umbilical Vein Endothelial Cells / drug effects
Humans
Promoter Regions, Genetic
Serum Response Factor / metabolism
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcriptional Activation
Vascular Endothelial Growth Factor A / pharmacology
p300-CBP Transcription Factors / genetics
p300-CBP Transcription Factors / metabolism*

Substances

Antigens, CD
Cadherins
Histones
MRTFA protein, human
Serum Response Factor
Trans-Activators
Vascular Endothelial Growth Factor A
cadherin 5
p300-CBP Transcription Factors
p300-CBP-associated factor