PMID:12011060

Citation	van Wering, HM, Huibregtse, IL, van der Zwan, SM, de Bie, MS, Dowling, LN, Boudreau, F, Rings, EH, Grand, RJ and Krasinski, SD (2002) Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter. J. Biol. Chem. 277:27659-67
Abstract	GATA-4, -5, and -6 zinc finger and hepatocyte nuclear factor-1alpha (HNF-1alpha) homeodomain transcription factors are expressed in the intestinal epithelium and synergistically activate the promoter of intestinal genes. Here, we demonstrate that GATA-5 and HNF-1alpha physically associate both in vivo and in vitro and that this interaction is necessary for cooperative activation of the lactase-phlorizin hydrolase promoter. Furthermore, physical association is mediated by the C-terminal zinc finger of GATA factors and the homeodomain of HNF-1alpha. Deletion of HNF-1alpha activation domains or interruption of HNF-1-binding sites in the lactase-phlorizin hydrolase promoter resulted in a complete loss of cooperativity, whereas deletion of GATA-5 activation domains or interruption of GATA-binding sites resulted in a reduction, but not an elimination, of cooperativity. We hypothesize that GATA/HNF-1alpha cooperativity is mediated by HNF-1alpha through its activation domains, which are oriented for high levels of activation through binding to DNA and physical association with GATA factors. These data suggest a paradigm whereby intestine-specific gene expression is regulated by unique interactions among tissue-restricted transcription factors coexpressed in the intestine. Parallel mechanisms in other tissues as well as in Drosophila suggest that zinc finger/homeodomain interactions are an efficient pathway of cooperative activation of gene transcription that has been conserved throughout evolution.
Links	PubMed Online version:10.1074/jbc.M203645200
Keywords	Base Sequence; DNA-Binding Proteins/metabolism; GATA5 Transcription Factor; Genetic Vectors; Glycosylceramidase/genetics; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Humans; Mutagenesis, Site-Directed; Nuclear Proteins; Promoter Regions, Genetic; Recombinant Proteins/metabolism; Restriction Mapping; Sequence Deletion; Transcription Factors/metabolism; Transcription, Genetic; Zinc Fingers
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