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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number21781
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation'. Together they form a unique fingerprint.

Cite this