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

Pier Lorenzo Puri, Simona Iezzi, Peter Stiegler, Tung Ti Chen, R. Louis Schiltz, George E O Muscat, Antonio Giordano, Larry Kedes, Jean Y J Wang, Vittorio Sartorelli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)885-897
Number of pages13
JournalMolecular Cell
Volume8
Issue number4
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Molecular Biology

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