Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis.
Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis.
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DOI：
10.1016/s1097-2765(01)00373-2
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发表时间：
2001-10
期刊：
影响因子：
16
通讯作者：
P. L. Puri;P. L. Puri;S. Iezzi;P. Stiegler;Tung-Ti Chen;R. Schiltz;G. Muscat;A. Giordano;L. Kedes;Jean Y. J. Wang;V. Sartorelli
中科院分区：
文献类型：
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作者：
P. L. Puri;P. L. Puri;S. Iezzi;P. Stiegler;Tung-Ti Chen;R. Schiltz;G. Muscat;A. Giordano;L. Kedes;Jean Y. J. Wang;V. Sartorelli
我们描述了生肌激活剂 MyoD、脱乙酰酶 HDAC1 和肿瘤抑制因子 pRb 之间的功能和生化联系。未分化成肌细胞中 MyoD 与 HDAC1 的相互作用介导肌肉特异性基因表达的抑制。通过血清去除模拟的促分化线索诱导 HDAC1 蛋白下调和 pRb 低磷酸化。 pRb 的去磷酸化促进分化肌管中 pRb-HDAC1 复合物的形成。 pRb-HDAC1 关联与 MyoD-HDAC1 复合物的分解、肌肉限制基因的转录激活以及骨骼肌成肌细胞的细胞分化同时发生。 pRb 的 HDAC1 结合域中引入的单点突变会损害其破坏 MyoD-HDAC1 相互作用和促进肌肉基因表达的能力。这些结果表明，HDAC1 表达的减少及其在替代核蛋白复合物中的重新分布对于骨骼肌细胞的终末分化至关重要。
We describe a functional and biochemical link between the myogenic activator MyoD, the deacetylase HDAC1, and the tumor suppressor pRb. Interaction of MyoD with HDAC1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression. Prodifferentiation cues, mimicked by serum removal, induce both downregulation of HDAC1 protein and pRb hypophosphorylation. Dephosphorylation of pRb promotes the formation of pRb-HDAC1 complex in differentiated myotubes. pRb-HDAC1 association coincides with disassembling of MyoD-HDAC1 complex, transcriptional activation of muscle-restricted genes, and cellular differentiation of skeletal myoblasts. A single point mutation introduced in the HDAC1 binding domain of pRb compromises its ability to disrupt MyoD-HDAC1 interaction and to promote muscle gene expression. These results suggest that reduced expression of HDAC1 accompanied by its redistribution in alternative nuclear protein complexes is critical for terminal differentiation of skeletal muscle cells.