Analysis of novel p300/GATA4 binding complex druing cardiomyocyte hypertrophy by proteomics approach

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A zinc finger protein GATA4 is associates with an intrinsic histone acetyltransferase p300 and regulates myocardial transcriptional activities in response to hypertrophic stimuli. We found that Retinoblastoma protein (Rb)-associated protein 48 and 46 (RbAp48/46) are novel component of the p300/GATA4 complex and form a repressor complex with HDACs in cardiomyocytes. RbAp48/46 could bind to GATA4, mediate the binding of HDAC1/2 with GATA4, and inhibited phenylephrine-induced hypertrophic responses such as acetylation of GATA4, activation of the ANF and ET-1 promoters, and increase in cell size. On the contrary, knockdown of RbAp48/46 by shRNA augmented such responses. Knockdown of HDAC1/2 augmented PE-induced hypertrophy and failed to inhibitory effects by RbAp48/46.These findings demonstrate that RbAp48/46 recruit HDAC1/2 onto GATA4, suppress the binding of p300 with GATA4, and inhibit hypertrophic responses in cardiomyocytes.