The Transcriptional Coactivator CAMTA2 Stimulates Cardiac Growth by Opposing Class II Histone Deacetylases

Kunhua Song, Johannes Backs, John McAnally, Xiaoxia Qi, Robert D. Gerard, James A Richardson, Joseph A Hill, Rhonda S Bassel-Duby, Eric N Olson

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Postnatal cardiac myocytes respond to diverse signals by hypertrophic growth and activation of a fetal gene program. In an effort to discover regulators of cardiac hypertrophy, we performed a eukaryotic expression screen for activators of the atrial natriuretic factor (ANF) gene, a cardiac-specific marker of hypertrophic signaling. We discovered that a family of transcriptional coactivators, called CAMTAs, promotes cardiomyocyte hypertrophy and activates the ANF gene, at least in part, by associating with the cardiac homeodomain protein Nkx2-5. The transcriptional activity of CAMTAs is governed by association with class II histone deacetylases (HDACs), which negatively regulate cardiac growth. Mice homozygous for a mutation in a CAMTA gene are defective in cardiac growth in response to pressure overload and neurohumoral signaling, whereas mice lacking HDAC5, a class II HDAC, are sensitized to the prohypertrophic actions of CAMTA. These findings reveal a transcriptional regulatory mechanism that modulates cardiac growth and gene expression by linking hypertrophic signals to the cardiac genome.

Original languageEnglish (US)
Pages (from-to)453-466
Number of pages14
JournalCell
Volume125
Issue number3
DOIs
StatePublished - May 5 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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