The CSRP2BP histone acetyltransferase drives smooth muscle gene expression.
The CSRP2BP histone acetyltransferase drives smooth muscle gene expression.
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CSRP2BP组蛋白乙酰转移酶驱动平滑肌基因表达
DOI：
10.1093/nar/gkw1227
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发表时间：
2017-04-07
影响因子：
14.9
通讯作者：
Schwartz RJ
中科院分区：
文献类型：
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作者：
Ma Y;Li Q;Li A;Wei Y;Long P;Jiang X;Sun F;Weiskirchen R;Wu B;Liang C;Grötzinger J;Wei Y;Yu W;Mercola M;Huang Y;Wang J;Yu Y;Schwartz RJ
几乎所有平滑肌基因的表达都是由其启动子区的血清反应因子结合位点控制的。然而，单独的SRF不足以调节平滑肌细胞发育。它与其他心血管特异性辅因子联合调节平滑肌基因表达。以前，我们发现转录辅因子CRP 2是平滑肌基因表达的调节因子。在这里，我们报告说，CSRP2BP，CRP 2的共激活剂，是一种组蛋白乙酰转移酶和平滑肌基因表达的驱动程序。CSRP2BP直接与SRF、CRP 2和myocardin相互作用。CSRP2BP以SRF依赖性方式协同激活平滑肌基因启动子。SRF、GATA6和CRP 2的组合需要CSRP2BP以获得稳健的平滑肌基因启动子活性。在平滑肌细胞中敲低Csrp2bp导致平滑肌基因表达减少。我们的结论是CSRP2BP组蛋白乙酰转移酶是CRP 2的共激活因子，与SRF和myocardin协同作用调节平滑肌基因表达。
The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression.