Histone acetyltransferase p300 promotes MRTF-A-mediates transactivation of VE-cadherin gene in human umbilical vein endothelial cells.
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.
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
Xiang-Zhu
XZ
Shu
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
Li-Nan
LN
Zhang
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
Rui
R
Zhang
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
Cai-Jiao
CJ
Zhang
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
Hong-Peng
HP
He
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
Hao
H
Zhou
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.
Nan
N
Wang
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.
Tong-Cun
TC
Zhang
D000107:Acetylation; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099152:Cadherin 5; D000099224:p300-CBP-Associated Factor
D015703:Antigens, CD; D015820:Cadherins; D006657:Histones; D026362:Serum Response Factor; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D050880:p300-CBP Transcription Factors; D000099152:Cadherin 5; D000099224:p300-CBP-Associated Factor; C431575:MRTFA protein, human
MRTF-A; Transcription regulation; VE-cadherin; p300