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

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, the GATA-4/DNA-binding, and transcriptional activities of GATA-4-dependent promoters in cardiac myocytes as well. These findings demonstrate that FOG-2 represses hypertrophic responses in cardiac myocytes and that p300 is involved in these repressive effects.

• Authors: Maretoshi Hirai, Koh Ono, Tatsuya Morimoto, Teruhisa Kawamura, Hiromichi Wada, Toru Kita, Koji Hasegawa
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 36 Pg. 37640-50 (Sep 03 2004) ISSN: 0021-9258 [Print] United States
• PMID: 15220332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• DNA-Binding Proteins
• GATA4 Transcription Factor
• Nuclear Proteins
• Trans-Activators
• Transcription Factors
• ZFPM2 protein, human
• E1A-Associated p300 Protein
• Ep300 protein, rat

Topics

• Animals
• Base Sequence
• Cells, Cultured
• DNA Primers
• DNA-Binding Proteins (metabolism, physiology)
• E1A-Associated p300 Protein
• Electrophoretic Mobility Shift Assay
• GATA4 Transcription Factor
• Heart (physiopathology)
• Nuclear Proteins (metabolism)
• Rats
• Trans-Activators (metabolism)
• Transcription Factors (metabolism, physiology)
• Transcription, Genetic (physiology)