Journal of Biological Chemistry
Volume 277, Issue 6, 8 February 2002, Pages 4519-4525
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GENES: STRUCTURE AND REGULATION
GATA-6 and Thyroid Transcription Factor-1 Directly Interact and Regulate Surfactant Protein-C Gene Expression*

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GATA-6, a member of the GATA family of zinc finger domain containing transcription factors, is expressed in endodermally derived tissues including the lung, where GATA-6 influences the transcription of target genes, TTF-1, and surfactant proteins. Whereas GATA-6 did not directly alter expression ofsp-C constructs in HeLa cells, GATA-6 synergistically activated sp-C gene transcription when co-expressed with TTF-1, supporting the concept that GATA-6 and TTF-1 might directly interact to influence target gene expression. GST-GATA-6 directly co-precipitated with TTF-1 after in vitrotranslation and directly interacted with the TTF-1-binding element in the sp-C promoter. Binding of TTF-1 to GATA-6 required the homeodomain of TTF-1, but optimal interactions with GATA-6 required the homeodomain and either carboxyl- or amino-terminal domains of TTF-1. Interactions between TTF-1 and GATA-6 required the amino-terminal and zinc finger domains of GATA-6. Although GATA-4 also interacted with TTF-1 in two-hybrid assays, GATA-4 was not as active as GATA-6 in the activation of the sp-C promoter with TTF-1. Deletion and substitution mutations between GATA-4 and GATA-6 demonstrated that the carboxyl-terminal zinc finger domain of GATA-6 contributed to its synergistic activation of the sp-C promoter with TTF-1. GATA-6 influenced the activity of the sp-C promoter, binding and acting synergistically with TTF-1.

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Published, JBC Papers in Press, December 3, 2001, DOI 10.1074/jbc.M107585200

*

This work was supported by National Institutes of Health Grants HL38859, HL56387 (to J. A. W.), and HL50046 (to S. W. G.).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.