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PMID: 10737771 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 8 ·2000-04-11 ·Pages 4070-5

Lu J, McKinsey TA, Nicol RL, Olson EN

Abstract

Myocyte enhancer factor-2 (MEF2) transcription factors control muscle-specific and growth factor-inducible genes. We show that hypertrophic growth of cardiomyocytes in response to phenylephrine and serum is accompanied by activation of MEF2 through a posttranslational mechanism mediated by calcium, calmodulin-dependent protein kinase (CaMK), and mitogen-activated protein kinase (MAPK) signaling. CaMK stimulates MEF2 activity by dissociating class II histone deacetylases (HDACs) from the DNA-binding domain. MAPKs, which activate MEF2 by phosphorylation of the transcription activation domain, maximally stimulate MEF2 activity only when repression by HDACs is relieved by CaMK signaling to the DNA-binding domain. These findings identify MEF2 as an endpoint for hypertrophic stimuli in cardiomyocytes and demonstrate that MEF2 mediates synergistic transcriptional responses to the CaMK and MAPK signaling pathways by signal-dependent dissociation from HDACs.

MeSH Terms
Animals Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cells, Cultured DNA-Binding Proteins/metabolism Histone Deacetylases/metabolism MEF2 Transcription Factors Mice Myogenic Regulatory Factors Rats Signal Transduction Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins MEF2 Transcription Factors Myogenic Regulatory Factors Transcription Factors Calcium-Calmodulin-Dependent Protein Kinases Histone Deacetylases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lu J
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75235-9148, USA.
McKinsey T A
Nicol R L
Olson E N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.080064097
Published
2000-04-11
Pages
4070-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18151
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.080064097 PMC Full Text View journal details
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