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

Jianrong Lu, Timothy A. McKinsey, Rebekka L. Nicol, Eric N. Olson

Research output: Contribution to journalArticle

370 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4070-4075
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number8
DOIs
StatePublished - Apr 11 2000

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MEF2 Transcription Factors
Histone Deacetylases
Transcription Factors
Calcium-Calmodulin-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
Cardiac Myocytes
DNA
Phenylephrine
Transcriptional Activation
Signal Transduction
Intercellular Signaling Peptides and Proteins
Phosphorylation
Muscles

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases. / Lu, Jianrong; McKinsey, Timothy A.; Nicol, Rebekka L.; Olson, Eric N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 8, 11.04.2000, p. 4070-4075.

Research output: Contribution to journalArticle

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