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PMID: 14517256 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differential role of p300 and CBP acetyltransferase during myogenesis: p300 acts upstream of MyoD and Myf5.

The EMBO journal ·Vol. 22 ·No. 19 ·2003-10-01 ·Pages 5186-96

Roth JF, Shikama N, Henzen C, Desbaillets I, Lutz W, Marino S, Wittwer J, Schorle H, Gassmann M, Eckner R

Abstract

Studies in tissue culture cells have implicated p300 and CBP acetyltransferases in myogenic regulatory factor (MRF) mediated transcription and terminal differentiation of skeletal muscle cells. However, in vivo data placing p300 and CBP on myogenic differentiation pathways are not yet available. In this report we provide genetic evidence that p300 but not CBP acetyltransferase (AT) activity is required for myogenesis in the mouse and in embryonic stem (ES) cells. A fraction of embryos carrying a single p300 AT- deficient allele exhibit impaired MRF expression, delayed terminal differentiation and a reduced muscle mass. In mouse embryos lacking p300 protein, Myf-5 induction is severely attenuated. Similarly, ES cells homozygous for a p300 AT or a p300 null mutation fail to activate Myf5 and MyoD transcription efficiently, while Pax3, acting genetically upstream of these MRFs, is expressed. In contrast, ES cells lacking CBP AT activity express MyoD and Myf5 and undergo myogenic differentiation. These data reveal a specific requirement for p300 and its AT activity in the induction of MRF gene expression and myogenic cell fate determination in vivo.

MeSH Terms
Acetyltransferases/deficiency,genetics,metabolism Animals CREB-Binding Protein Cell Cycle Proteins/genetics,metabolism DNA-Binding Proteins Histone Acetyltransferases Mice Mice, Knockout Muscle Development/genetics,physiology Muscle Proteins/metabolism MyoD Protein/metabolism Myogenic Regulatory Factor 5 Nuclear Proteins/deficiency,genetics,metabolism Stem Cells Trans-Activators/deficiency,genetics,metabolism Transcription Factors p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Muscle Proteins Myf5 protein, mouse MyoD Protein Myogenic Regulatory Factor 5 Nuclear Proteins Trans-Activators Transcription Factors Acetyltransferases CREB-Binding Protein Crebbp protein, mouse Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Roth Jeanne-Françoise
Institute of Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Shikama Noriko
Henzen Clea
Desbaillets Isabelle
Lutz Werner
Marino Silvia
Wittwer Jonas
Schorle Hubert
Gassmann Max
Eckner Richard
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg473
Published
2003-10-01
Pages
5186-96
Language
English
Region
England
NLM ID
8208664
PMCID
PMC204457
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg473 PMC Full Text View journal details
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