TY - JOUR
T1 - The Transcriptional Coactivator CAMTA2 Stimulates Cardiac Growth by Opposing Class II Histone Deacetylases
AU - Song, Kunhua
AU - Backs, Johannes
AU - McAnally, John
AU - Qi, Xiaoxia
AU - Gerard, Robert D.
AU - Richardson, James A
AU - Hill, Joseph A
AU - Bassel-Duby, Rhonda S
AU - Olson, Eric N
N1 - Funding Information:
We are grateful to John Shelton for assistance with histology and Yongli Kong, Meng Zhao, and Julie Poirot for technical help. We thank Zhigao Wang, Jay Schneider, Jens Fielitz, Zhiping Liu, and Shijie Li for helpful discussions and Tim McKinsey and Osamu Nakagawa for comments on the manuscript. We thank Alisha Tizenor for graphics and Jennifer Brown for editorial assistance. This work was supported by grants from the NIH, the Donald W. Reynolds Cardiovascular Clinical Research Center, and the Robert A. Welch Foundation to E.N.O. and the Deutsche Forschungsgemeinschaft (BA 2258/1-1) to J.B.
PY - 2006/5/5
Y1 - 2006/5/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2006.02.048
DO - 10.1016/j.cell.2006.02.048
M3 - Article
C2 - 16678093
AN - SCOPUS:33646144852
SN - 0092-8674
VL - 125
SP - 453
EP - 466
JO - Cell
JF - Cell
IS - 3
ER -