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