Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding activity, transcriptional activity, and myogenic differentiation
Myocyte enhancer factor 2 acetylation by p300 enhances its DNA binding activity, transcriptional activity, and myogenic differentiation
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DOI：
10.1128/mcb.25.9.3575-3582.2005
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Wu, ZG
中科院分区：
文献类型：
--
作者：
Ma, KW;Chan, JKL;Wu, ZG
肌细胞增强因子2 （MEF2）家族蛋白是控制肌细胞、淋巴细胞和神经元基因表达的关键转录因子。已知MEF2蛋白受磷酸化调节。我们现在提供的证据表明MEF2C在体内和体外都被p300乙酰化。在C2C12肌源性细胞中，MEF2在分化的肌细胞中优先发生乙酰化，而在未分化的成肌细胞中不发生乙酰化。几个主要的乙酰化位点被映射到MEF2C的反活化结构域，其中一些在几个不同物种的其他MEF2成员中是完全保守的。这些赖氨酸的突变影响MEF2 DNA的结合和转录活性，以及它与肌生成素在肌生成转化试验中的协同作用。当引入C2C12成肌细胞时，不可乙酰化的MEF2C抑制肌源性分化。因此，除了磷酸化，MEF2活性在肌发生过程中也受到乙酰化的关键调节。
Myocyte enhancer factor 2 (MEF2) family proteins are key transcription factors controlling gene expression in myocytes, lymphocytes, and neurons. MEF2 proteins are known to be regulated by phosphorylation. We now provide evidence showing that MEF2C is acetylated by p300 both in vitro and in vivo. In C2C12 myogenic cells, MEF2 is preferentially acetylated in differentiating myocytes but not in undifferentiated myoblasts. Several major acetylation sites are mapped to the transactivation domain of MEF2C, some of which are fully conserved in other MEF2 members from several different species. Mutation of these lysines affects MEF2 DNA binding and transcriptional activity, as well as its synergistic effect with myogenin in myogenic conversion assays. When introduced into C2C12 myoblasts, the nonacetylatable MEF2C inhibits myogenic differentiation. Thus, in addition to phosphorylation, MEF2 activity is also critically regulated by acetylation during myogenesis.