p300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription

Pier Lorenzo Puri, Maria Laura Avantaggiati, Clara Balsano, Nianli Sang, Adolf Graessmann, Antonio Giordano, Massimo Levrero

Research output: Contribution to journalArticle

Abstract

The nuclear phosphoprotein p300 is a new member of a family of 'co-activators' (which also includes the CREB binding protein CBP), that directly modulate transcription by interacting with components of the basal transcriptional machinery. Both p300 and CBP are targeted by the adenovirus E1A protein, and binding to p300 is required for E1A to inhibit terminal differentiation in both keratinocytes and myoblasts. Here we demonstrate that, in differentiating skeletal muscle cells, p300 physically interacts with the myogenic basic helix-loop-helix (bHLH) regulatory protein MyoD at its DNA binding sites. During muscle differentiation, MyoD plays a dual role: besides activating muscle-specific transcription, it induces permanent cell cycle arrest by up-regulating the cyclin-dependent kinase inhibitor p21. We show that p300 is involved in both these activities. Indeed, E1A mutants lacking the ability to bind p300 are greatly impaired in the repression of E-box-driven transcription, and p300 overexpression rescues the wild-type E1A-mediated repression. Moreover, p300 potentiates MyoD- and myogenin-dependent activation of transcription from E-box-containing reporter genes. We also provide evidence, obtained by microinjection of anti-p300 antibodies, that p300 is required for MyoD-dependent cell cycle arrest in either myogenic cells induced to differentiate or in MyoD-converted C3H10T1/2 fibroblasts, but is dispensable for maintenance of the post-mitotic state of myotubes.

Original languageEnglish
Pages (from-to)369-383
Number of pages15
JournalEMBO Journal
Volume16
Issue number2
DOIs
Publication statusPublished - Jan 15 1997

Keywords

  • Cell cycle arrest
  • E1A
  • MyoD
  • p300
  • Skeletal muscle

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Puri, P. L., Avantaggiati, M. L., Balsano, C., Sang, N., Graessmann, A., Giordano, A., & Levrero, M. (1997). p300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription. EMBO Journal, 16(2), 369-383. https://doi.org/10.1093/emboj/16.2.369