Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation
Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation
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DOI：
10.1038/sj.emboj.7601229
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发表时间：
2006-07-26
期刊：
影响因子：
11.4
通讯作者：
Mal, Asoke K.
中科院分区：
文献类型：
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作者：
Mal, Asoke K.
Suv 39 h1是一种组蛋白H3赖氨酸-9（H3-K9）特异性甲基转移酶（HMT），通过染色质修饰与基因沉默相关。肌细胞从增殖到分化的转变伴随着先前沉默的肌肉基因的转录激活。我报告Suv 39 h1与肌原性调节因子MyoD在增殖肌细胞中的相互作用，以及其与MyoD相关的HMT活性，随着分化的进行而减少。Suv 39 h1-MyoD复合物在沉默分化信号肌肉基因肌细胞生成素的染色质调节区被检测到，并且Suv 39 h1的存在与H3-K9甲基化相关。Suv 39 h1表达的增加抑制了MyoD依赖性肌肉基因的表达，这种特性需要其HMT活性。这种抑制需要Suv 39 h1与MyoD的结合以及肌细胞生成素启动子上H3-K9的持续甲基化。Suv 39 h1是肌肉基因阻遏所必需的，因为其被siRNA废除激活了MyoD的这些基因表达。这些发现表明，Suv 39 h1与肌肉基因启动子上的MyoD相关的存在使基因转录沉默，从而在增殖和分化之间提供必要的检查点。
Suv39h1 is a histone H3 lysine-9 (H3-K9) specific methyltransferase (HMT) that is associated with gene silencing through chromatin modification. The transition from proliferation into differentiation of muscle cell is accompanied by transcriptional activation of previously silent muscle genes. I report Suv39h1 interaction with myogenic regulator MyoD in proliferating muscle cells and its HMT activity, which is associated with MyoD, diminishes as differentiation proceeds. The Suv39h1-MyoD complex was detected on the chromatin regulatory regions of a silent differentiation signal muscle gene myogenin and that Suv39h1 presence correlated with H3-K9 methylation. Increased Suv39h1 expression repressed MyoD-dependent muscle gene expression and this property required its HMT activity. This repression required Suv39h1 association with MyoD as well as sustained methylation of H3-K9 on myogenin promoter. Suv39h1 was required for muscle gene repression because its abrogation by siRNA activates these gene expressions by MyoD. These findings suggest that Suv39h1 presence in association with MyoD on the promoter of muscle genes silences gene transcription, providing a necessary checkpoint between proliferation and differentiation.