GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression.
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.
Liu
Cong
C
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Glasser
Stephan W
SW
Wan
Huajing
H
Whitsett
Jeffrey A
JA
D000818:Animals; D001483:Base Sequence; D004247:DNA; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D050993:GATA6 Transcription Factor; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000502:physiology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C494760:Gata6 protein, mouse; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D004247:DNA