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Molecular and Cellular Biology, October 2000, p. 7550-7558, Vol. 20, No. 20
Department of Molecular and Cellular
Biology, Baylor College of Medicine, Houston, Texas
77030,1 and Laboratoire de
Développement et Différenciation Cardiaques, Institut de
Recherches Cliniques de Montréal, Montréal,
Québec, Canada H2W 1R72
Received 29 March 2000/Returned for modification 17 May
2000/Accepted 12 June 2000
Combinatorial interaction among cardiac tissue-restricted enriched
transcription factors may facilitate the expression of cardiac
tissue-restricted genes. Here we show that the MADS box factor serum
response factor (SRF) cooperates with the zinc finger protein GATA-4 to
synergistically activate numerous myogenic and nonmyogenic serum
response element (SRE)-dependent promoters in CV1 fibroblasts. In the
absence of GATA binding sites, synergistic activation depends on
binding of SRF to the proximal CArG box sequence in the cardiac and
skeletal
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Copyright © 2000, American Society for Microbiology. All rights reserved.
Cardiac Tissue Enriched Factors Serum Response
Factor and GATA-4 Are Mutual Coregulators
-actin promoter. GATA-4's C-terminal activation domain is
obligatory for synergistic coactivation with SRF, and its N-terminal
domain and first zinc finger are inhibitory. SRF and GATA-4 physically
associate both in vivo and in vitro through their MADS box and the
second zinc finger domains as determined by protein A pullout assays
and by in vivo one-hybrid transfection assays using Gal4 fusion
proteins. Other cardiovascular tissue-restricted GATA factors, such as
GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating
SRE-dependent targets. Thus, interaction between the MADS box and C4
zinc finger proteins, a novel regulatory paradigm, mediates activation
of SRF-dependent gene expression.
*
Corresponding author. Mailing address: Department of
Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6649. Fax: (713) 798-7799. E-mail: schwartz{at}bcm.tmc.edu.
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