FOG-2 competes with GATA-4 for transcriptional coactivator p300 and represses hypertrophic responses in cardiac myocytes.

The Journal of Biological Chemistry
Maretoshi HiraiKoji Hasegawa

Abstract

A multizinc finger protein, FOG-2, associates with a cardiac transcription factor, GATA-4, and represses GATA-4-dependent transcription. GATA-4 is required not only for normal heart development but is also involved in hypertrophic responses in cardiac myocytes; however, the effects of FOG-2 on these responses are unknown. The interaction of GATA-4 with a transcriptional coactivator p300 is required for its full transcriptional activity and the activation of the embryonic program during myocardial cell hypertrophy. We show here that exogenous FOG-2 represses phenylephrine-induced hypertrophic responses such as myofibrillar organization, increases in cell size, and hypertrophy-associated gene transcription. Using immunoprecipitation Western blotting, we demonstrate that FOG-2 physically interacted with p300 and reduced the binding of GATA-4 to p300. In addition, in COS7 cells, in which the function of endogenous p300 is disrupted, FOG-2 is unable to repress the GATA-4-dependent transcriptional activities; however, FOG-2 markedly repressed the p300-mediated increase in the DNA-binding and transcriptional activities of GATA-4 in these cells. Similarly, FOG-2 inhibited a phenylephrine-induced increase in the p300/GATA-4 interaction,...Continue Reading

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Citations

Apr 9, 2008·Biochemistry. Biokhimii︠a︡·Bin ZhengJin-Kun Wen
Feb 23, 2008·The Journal of Clinical Investigation·Tatsuya MorimotoKoji Hasegawa
Dec 8, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Yoshinori YoshidaKoji Hasegawa
Jul 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mei XinEric N Olson
Mar 9, 2010·Life Sciences·Jessica MwinyiMagnus Ingelman-Sundberg
Jan 22, 2005·Seminars in Cell & Developmental Biology·Alan B Cantor, Stuart H Orkin
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Jul 2, 2015·Cellular and Molecular Life Sciences : CMLS·Sonia Stefanovic, Vincent M Christoffels
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