GATA-4 Activates Transcription Via Two Novel Domains That Are Conserved within the GATA-4/5/6 Subfamily*
- ‡ Established Investigator of the American Heart Association. To whom correspondence should be addressed: Dept. of Medicine, University of Chicago, MC 6088, 5841 S. Maryland Ave., Chicago, IL 60637. Tel.: 312-702-2679; Fax: 312-702-2681.
Abstract
GATA-4 is one of the earliest developmental markers of the precardiac mesoderm, heart, and gut and has been shown to activate regulatory elements controlling transcription of genes encoding cardiac-specific proteins. To elucidate the molecular mechanisms underlying the transcriptional activity of the GATA-4 protein, structure-function analyses were performed. These analyses revealed that the C-terminal zinc finger and adjacent basic domain of GATA-4 is bifunctional, modulating both DNA-binding and nuclear localization activities. The N terminus of the protein encodes two independent transcriptional Activation Domains (amino acids 1-74 and amino acids 130-177). Amino acid residues were identified within each domain that are required for transcriptional activation. Finally, we have shown that regions of Xenopus GATA-5 and −6 corresponding to Activation Domains I and II, respectively, function as potent transcriptional activators. The identification and functional characterization of two evolutionarily conserved transcriptional Activation Domains within the GATA-4/5/6 subfamily suggests that each of these domains modulates critical functions in the transcriptional regulatory program(s) encoded by GATA-4, −5, and −6 during vertebrate development. As such these data provide novel insights into the molecular mechanisms that control development of the heart.
Footnotes
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↵* This work was supported in part by Public Health Service Grant 1R01HL51145 and an American Heart Association Grant-In-Aid (to M. S. P.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- aa
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amino acid(s)
- PCR
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polymerase chain reaction
- cTnC
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cardiac troponin C
- DBD
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DNA binding domain
- GH
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growth hormone
- EMSA
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electrophoretic mobility shift assay
- Act I and Act II
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Activation Domain I and II, respectively.
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↵2H. Ip, E. Morrisey, and M. Parmacek, unpublished observations.
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- Received December 26, 1996.
- Revision received January 21, 1997.
- © 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
