Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases
Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases
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DOI：
10.1016/s1097-2765(00)00025-3
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发表时间：
2000-08-01
期刊：
影响因子：
16
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Lu, JR;McKinsey, TA;Olson, EN
骨骼肌分化受肌源性碱性螺旋环螺旋和MEF2转录因子之间的关联控制。我们发现，与这些转录因子调控的肌肉基因相关的染色质在肌肉形成过程中发生乙酰化，而与MEF2相互作用的II类组蛋白去乙酰化酶（hdac）特异性地抑制成肌细胞分化。这些hdac不直接与MyoD相互作用，但它们通过与MEF2的关联抑制MyoD的肌生成活性。提高MyoD水平可以克服hdac对肌肉基因的抑制作用。hdac介导的肌生成抑制也可以通过CaM激酶和胰岛素样生长因子（IGF）信号传导来克服。这些发现揭示了hdac在肌发生过程中染色质重塑中的核心作用，以及作为IGF和CaM激酶控制的信号通路的核内靶点。
Skeletal muscle differentiation is controlled by associations between myogenic basic-helix-loop-helix and MEF2 transcription factors. We show that chromatin associated with muscle genes regulated by these transcription factors becomes acetylated during myogenesis and that class II histone deacetylases (HDACs), which interact with MEF2, specifically suppress myoblast differentiation. These HDACs do not interact directly with MyoD, yet they suppress its myogenic activity through association with MEF2. Elevating the level of MyoD can override the repression imposed by HDACs on muscle genes. HDAC-mediated repression of myogenesis also can be overcome by CaM kinase and insulin-like growth factor (IGF) signaling. These findings reveal central roles for HDACs in chromatin remodeling during myogenesis and as intranuclear targets far signaling pathways controlled by IGF and CaM kinase.