YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation

Abstract Yin Yang 1 (YY1) regulates gene transcription in a variety of biological processes. In this study, we aim to determine the role of YY1 in vascular smooth muscle cell (VSMC) phenotypic modulation both in vivo and in vitro. Here we show that vascular injury in rodent carotid arteries induces...

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Autores principales:	Jian-Pu Zheng, Xiangqin He, Fang Liu, Shuping Yin, Shichao Wu, Maozhou Yang, Jiawei Zhao, Xiaohua Dai, Hong Jiang, Luyi Yu, Qin Yin, Donghong Ju, Claire Li, Leonard Lipovich, Youming Xie, Kezhong Zhang, Hui J. Li, Jiliang Zhou, Li Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc7f4842bb50449f8d66b93adfce802c
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spelling	oai:doaj.org-article:cc7f4842bb50449f8d66b93adfce802c2021-12-02T15:11:52ZYY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation10.1038/s41598-020-78544-32045-2322https://doaj.org/article/cc7f4842bb50449f8d66b93adfce802c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78544-3https://doaj.org/toc/2045-2322Abstract Yin Yang 1 (YY1) regulates gene transcription in a variety of biological processes. In this study, we aim to determine the role of YY1 in vascular smooth muscle cell (VSMC) phenotypic modulation both in vivo and in vitro. Here we show that vascular injury in rodent carotid arteries induces YY1 expression along with reduced expression of smooth muscle differentiation markers in the carotids. Consistent with this finding, YY1 expression is induced in differentiated VSMCs in response to serum stimulation. To determine the underlying molecular mechanisms, we found that YY1 suppresses the transcription of CArG box-dependent SMC-specific genes including SM22α, SMα-actin and SMMHC. Interestingly, YY1 suppresses the transcriptional activity of the SM22α promoter by hindering the binding of serum response factor (SRF) to the proximal CArG box. YY1 also suppresses the transcription and the transactivation of myocardin (MYOCD), a master regulator for SMC-specific gene transcription by binding to SRF to form the MYOCD/SRF/CArG box triad (known as the ternary complex). Mechanistically, YY1 directly interacts with MYOCD to competitively displace MYOCD from SRF. This is the first evidence showing that YY1 inhibits SMC differentiation by directly targeting MYOCD. These findings provide new mechanistic insights into the regulatory mechanisms that govern SMC phenotypic modulation in the pathogenesis of vascular diseases.Jian-Pu ZhengXiangqin HeFang LiuShuping YinShichao WuMaozhou YangJiawei ZhaoXiaohua DaiHong JiangLuyi YuQin YinDonghong JuClaire LiLeonard LipovichYouming XieKezhong ZhangHui J. LiJiliang ZhouLi LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jian-Pu Zheng Xiangqin He Fang Liu Shuping Yin Shichao Wu Maozhou Yang Jiawei Zhao Xiaohua Dai Hong Jiang Luyi Yu Qin Yin Donghong Ju Claire Li Leonard Lipovich Youming Xie Kezhong Zhang Hui J. Li Jiliang Zhou Li Li YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
description	Abstract Yin Yang 1 (YY1) regulates gene transcription in a variety of biological processes. In this study, we aim to determine the role of YY1 in vascular smooth muscle cell (VSMC) phenotypic modulation both in vivo and in vitro. Here we show that vascular injury in rodent carotid arteries induces YY1 expression along with reduced expression of smooth muscle differentiation markers in the carotids. Consistent with this finding, YY1 expression is induced in differentiated VSMCs in response to serum stimulation. To determine the underlying molecular mechanisms, we found that YY1 suppresses the transcription of CArG box-dependent SMC-specific genes including SM22α, SMα-actin and SMMHC. Interestingly, YY1 suppresses the transcriptional activity of the SM22α promoter by hindering the binding of serum response factor (SRF) to the proximal CArG box. YY1 also suppresses the transcription and the transactivation of myocardin (MYOCD), a master regulator for SMC-specific gene transcription by binding to SRF to form the MYOCD/SRF/CArG box triad (known as the ternary complex). Mechanistically, YY1 directly interacts with MYOCD to competitively displace MYOCD from SRF. This is the first evidence showing that YY1 inhibits SMC differentiation by directly targeting MYOCD. These findings provide new mechanistic insights into the regulatory mechanisms that govern SMC phenotypic modulation in the pathogenesis of vascular diseases.
format	article
author	Jian-Pu Zheng Xiangqin He Fang Liu Shuping Yin Shichao Wu Maozhou Yang Jiawei Zhao Xiaohua Dai Hong Jiang Luyi Yu Qin Yin Donghong Ju Claire Li Leonard Lipovich Youming Xie Kezhong Zhang Hui J. Li Jiliang Zhou Li Li
author_facet	Jian-Pu Zheng Xiangqin He Fang Liu Shuping Yin Shichao Wu Maozhou Yang Jiawei Zhao Xiaohua Dai Hong Jiang Luyi Yu Qin Yin Donghong Ju Claire Li Leonard Lipovich Youming Xie Kezhong Zhang Hui J. Li Jiliang Zhou Li Li
author_sort	Jian-Pu Zheng
title	YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
title_short	YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
title_full	YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
title_fullStr	YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
title_full_unstemmed	YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
title_sort	yy1 directly interacts with myocardin to repress the triad myocardin/srf/carg box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/cc7f4842bb50449f8d66b93adfce802c
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YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation

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