Regulation of HDAC9 gene expression by MEF2 establishes a negative-feedback loop in the transcriptional circuitry of muscle differentiation
Regulation of HDAC9 gene expression by MEF2 establishes a negative-feedback loop in the transcriptional circuitry of muscle differentiation
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DOI：
10.1128/mcb.01415-06
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Olson, Eric N.
中科院分区：
文献类型：
--
作者：
Haberland, Michael;Arnold, Michael A.;Olson, Eric N.
骨骼肌发育受肌细胞增强因子（MEF 2）和生肌碱性螺旋-环-螺旋（bHLH）转录因子家族控制，其关联并协同激活肌肉基因表达。肌肉分化通过正反馈回路进一步加强，其中肌源性bHLH蛋白激活其自身的表达和MEF 2的表达，而MEF 2刺激肌源性bHLH基因和Mef 2c基因的表达。在这里，我们描述了一个肌源性负反馈环，由MEF 2蛋白和转录抑制因子组蛋白去乙酰化酶9（HDAC 9）。我们表明，HDAC 9基因是MEF 2在体外和体内的直接转录靶点。HDAC 9可以与MEF 2蛋白结合并抑制其转录活性。因此，转录抑制因子HDAC 9在肌肉分化的转录回路中形成负反馈环。
Skeletal muscle development is controlled by the myocyte enhancer factor (MEF2) and myogenic basic helix-loop-helix (bHLH) families of transcription factors, which associate and synergistically activate muscle gene expression. Muscle differentiation is further reinforced by positive-feedback loops in which myogenic bHLH proteins activate their own expression and the expression of MEF2, while MEF2 stimulates expression of myogenic bHLH genes and the Mef2c gene. Here we describe a myogenic negative-feedback loop that consists of MEF2 proteins and the transcriptional repressor histone deacetylase 9 (HDAC9). We show that the HDAC9 gene is a direct transcriptional target of MEF2 in vitro and in vivo. HDAC9 can associate with MEF2 proteins and suppress their transcriptional activity. The transcriptional repressor HDAC9 thus forms a negative-feedback loop in the transcriptional circuitry of muscle differentiation.