title: The transcriptional coactivator CAMTA2 stimulates cardiac growth by opposing class II histone deacetylases.
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.
authors: Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd., Dallas, TX 75390, USA.
authors: Kunhua
authors: K
authors: Song
authors: Johannes
authors: J
authors: Backs
authors: John
authors: J
authors: McAnally
authors: Xiaoxia
authors: X
authors: Qi
authors: Robert D
authors: RD
authors: Gerard
authors: James A
authors: JA
authors: Richardson
authors: Joseph A
authors: JA
authors: Hill
authors: Rhonda
authors: R
authors: Bassel-Duby
authors: Eric N
authors: EN
authors: Olson