Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis

We describe a functional and biochemical link between the myogenic activato r MyoD, the deacetylase HDAC1, and the tumor suppressor pRb. Interaction of MyoD with HDAC1 in undifferentiated myoblasts mediates repression of muscl e-specific gene expression. Prodifferentiation cues, mimicked by serum remo val, induce both downregulation of HDAC1 protein and pRb hypophosphorylatio n. 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 gen es, and cellular differentiation of skeletal myoblasts. A single point muta tion introduced in the HDAC1 binding domain of pRb compromises its ability to disrupt MyoD-HDAC1 interaction and to promote muscle gene expression. Th ese results suggest that reduced expression of HDAC1 accompanied by its red istribution in alternative nuclear protein complexes is critical for termin al differentiation of skeletal muscle cells.