Cargando…

Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis

The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cel...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Jiahuan, Liang, Xiaodong, Zhang, Shasha, Wang, Shiyan, Garcia, Sara P., Yan, Pengyi, Yu, Huijing, Li, Zixuan, Liu, Li, Zhang, Fang, Wei, Weiting, Le, Huangying, Zhang, Yan, Yuan, Guo-cheng, Chen, Sun, Chen, Yingwei, Sun, Kun, Pu, William T., Zhang, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992747/
https://www.ncbi.nlm.nih.gov/pubmed/32001672
http://dx.doi.org/10.1038/s41419-020-2228-3
_version_ 1783492897414316032
author Chen, Jiahuan
Liang, Xiaodong
Zhang, Shasha
Wang, Shiyan
Garcia, Sara P.
Yan, Pengyi
Yu, Huijing
Li, Zixuan
Liu, Li
Zhang, Fang
Wei, Weiting
Le, Huangying
Zhang, Yan
Yuan, Guo-cheng
Chen, Sun
Chen, Yingwei
Sun, Kun
Pu, William T.
Zhang, Bing
author_facet Chen, Jiahuan
Liang, Xiaodong
Zhang, Shasha
Wang, Shiyan
Garcia, Sara P.
Yan, Pengyi
Yu, Huijing
Li, Zixuan
Liu, Li
Zhang, Fang
Wei, Weiting
Le, Huangying
Zhang, Yan
Yuan, Guo-cheng
Chen, Sun
Chen, Yingwei
Sun, Kun
Pu, William T.
Zhang, Bing
author_sort Chen, Jiahuan
collection PubMed
description The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA (vascular endothelial growth factor A) stimulation, we discovered that BDs are widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The BDs responsive to VEGFA have more permissive chromatin environment comparing to other BDs. The initial activation of bivalent genes depends on RNAPII pausing release induced by EZH1 rather than removal of H3K27me3. The later suppression of bivalent gene expression depended on KDM5A recruitment by its interaction with PRC2. Importantly, EZH1 promoted both in vitro and in vivo angiogenesis by upregulating EGR3, whereas KDM5A dampened angiogenesis. Collectively, this study demonstrates a novel dual function of BDs in endothelial cells to control VEGF responsiveness and angiogenesis.
format Online
Article
Text
id pubmed-6992747
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-69927472020-01-31 Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis Chen, Jiahuan Liang, Xiaodong Zhang, Shasha Wang, Shiyan Garcia, Sara P. Yan, Pengyi Yu, Huijing Li, Zixuan Liu, Li Zhang, Fang Wei, Weiting Le, Huangying Zhang, Yan Yuan, Guo-cheng Chen, Sun Chen, Yingwei Sun, Kun Pu, William T. Zhang, Bing Cell Death Dis Article The bivalent domain (BD) at promoter region is an unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of BDs in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA (vascular endothelial growth factor A) stimulation, we discovered that BDs are widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The BDs responsive to VEGFA have more permissive chromatin environment comparing to other BDs. The initial activation of bivalent genes depends on RNAPII pausing release induced by EZH1 rather than removal of H3K27me3. The later suppression of bivalent gene expression depended on KDM5A recruitment by its interaction with PRC2. Importantly, EZH1 promoted both in vitro and in vivo angiogenesis by upregulating EGR3, whereas KDM5A dampened angiogenesis. Collectively, this study demonstrates a novel dual function of BDs in endothelial cells to control VEGF responsiveness and angiogenesis. Nature Publishing Group UK 2020-01-30 /pmc/articles/PMC6992747/ /pubmed/32001672 http://dx.doi.org/10.1038/s41419-020-2228-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Jiahuan
Liang, Xiaodong
Zhang, Shasha
Wang, Shiyan
Garcia, Sara P.
Yan, Pengyi
Yu, Huijing
Li, Zixuan
Liu, Li
Zhang, Fang
Wei, Weiting
Le, Huangying
Zhang, Yan
Yuan, Guo-cheng
Chen, Sun
Chen, Yingwei
Sun, Kun
Pu, William T.
Zhang, Bing
Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
title Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
title_full Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
title_fullStr Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
title_full_unstemmed Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
title_short Two faces of bivalent domain regulate VEGFA responsiveness and angiogenesis
title_sort two faces of bivalent domain regulate vegfa responsiveness and angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992747/
https://www.ncbi.nlm.nih.gov/pubmed/32001672
http://dx.doi.org/10.1038/s41419-020-2228-3
work_keys_str_mv AT chenjiahuan twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT liangxiaodong twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT zhangshasha twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT wangshiyan twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT garciasarap twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT yanpengyi twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT yuhuijing twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT lizixuan twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT liuli twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT zhangfang twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT weiweiting twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT lehuangying twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT zhangyan twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT yuanguocheng twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT chensun twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT chenyingwei twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT sunkun twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT puwilliamt twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis
AT zhangbing twofacesofbivalentdomainregulatevegfaresponsivenessandangiogenesis