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. 2002 Feb 8;277(6):4519-25.
doi: 10.1074/jbc.M107585200. Epub 2001 Dec 3.

GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression

Cong Liu  1 , Stephan W Glasser, Huajing Wan, Jeffrey A Whitsett
Affiliations
Free article

GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression

Cong Liu et al. J Biol Chem. .
Free article

Abstract

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 of sp-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 vitro translation 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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