YY1 directly interacts with myocardin to repress the triad myocardin/SRF/CArG box-mediated smooth muscle gene transcription during smooth muscle phenotypic modulation.
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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DOI：
10.1038/s41598-020-78544-3
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发表时间：
2020-12-11
影响因子：
4.6
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Zheng JP;He X;Liu F;Yin S;Wu S;Yang M;Zhao J;Dai X;Jiang H;Yu L;Yin Q;Ju D;Li C;Lipovich L;Xie Y;Zhang K;Li HJ;Zhou J;Li L
阴阳1 （YY1）在多种生物过程中调控基因转录。在本研究中，我们旨在确定YY1在体内和体外血管平滑肌细胞（VSMC）表型调节中的作用。本研究表明，啮齿动物颈动脉血管损伤诱导YY1表达，同时颈动脉平滑肌分化标志物表达减少。与这一发现一致，YY1的表达在分化的VSMCs中被诱导以响应血清刺激。为了确定潜在的分子机制，我们发现YY1抑制CArG盒依赖性smc特异性基因的转录，包括SM22α， SMα-actin和SMMHC。有趣的是，YY1通过阻碍血清反应因子（SRF）与近端CArG盒的结合来抑制SM22α启动子的转录活性。YY1还通过与SRF结合形成心肌蛋白/SRF/CArG三联体（称为三元复合物），抑制心肌蛋白（心肌蛋白是smc特异性基因转录的主要调节因子）的转录和反激活。在机制上，YY1直接与心肌相互作用，竞争性地取代SRF中的心肌。这是首次证明YY1通过直接靶向心肌抑制SMC分化的证据。这些发现为血管疾病发病机制中SMC表型调节的调控机制提供了新的机制见解。
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.
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影响因子：
4.6
作者：
Creemers, Esther E.;Sutherland, Lillian B.;Olson, Eric N.
通讯作者：
Olson, Eric N.
DOI：
10.1161/01.atv.17.10.2238
发表时间：
1997-10-01
影响因子：
8.7
作者：
Kumar, A;Lindner, V
通讯作者：
Lindner, V
影响因子：
4.8
作者：
Liu, Fang;Wang, Xiaobo;Zhou, Jiliang
通讯作者：
Zhou, Jiliang
影响因子：
5
作者：
Chen, JY;Kitchen, CM;Miano, JM
通讯作者：
Miano, JM
影响因子：
3.7
作者：
Dai, Xiaohua;Thiagarajan, Devi;Li, Li
通讯作者：
Li, Li