Journal article
p300 is required for MyoD‐dependent cell cycle arrest and muscle‐specific gene transcription
The EMBO journal, v 16(2), pp 369-383
15 Jan 1997
PMID: 9029156
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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.
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Details
- Title
- p300 is required for MyoD‐dependent cell cycle arrest and muscle‐specific gene transcription
- Creators
- Pier Lorenzo Puri - Istituto I Clinica Medica, Policlinico Umberto I, Università degli Studi di Roma La SapienzaMaria Laura Avantaggiati - DCBOC/Path, National Cancer Institute, National Institutes of HealthClara Balsano - Dipartimento di Medicina Interna, Università degli Studi di L'AquilaNianli Sang - Sbarro Institute for Cancer Research and Molecular Medicine and Department of Microbiology/Immunology, Thomas Jefferson UniversityAdolf Graessmann - Institut fur Molekularbiologie und Biochemie der Freien Universitat BerlinAntonio Giordano - Sbarro Institute for Cancer Research and Molecular Medicine and Department of Microbiology/Immunology, Thomas Jefferson UniversityMassimo Levrero - Istituto di Medicina Interna, Università di Cagliari
- Publication Details
- The EMBO journal, v 16(2), pp 369-383
- Publisher
- John Wiley & Sons, Ltd; Chichester, UK
- Number of pages
- 15
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:A1997WF38000015
- Scopus ID
- 2-s2.0-0031023139
- Other Identifier
- 991014877980204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology