title: Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic enhancer.
abstract: The embryonic endoderm is a multipotent progenitor cell population that gives rise to the epithelia of the digestive and respiratory tracts, the liver and the pancreas. Among the transcription factors that have been shown to be important for endoderm development and gut morphogenesis is GATA4. Despite the important role of GATA4 in endoderm development, its transcriptional regulation is not well understood. In this study, we identified an intronic enhancer from the mouse Gata4 gene that directs expression to the definitive endoderm in the early embryo. The activity of this enhancer is initially broad in all endodermal progenitors, as demonstrated by fate mapping analysis using the Cre/loxP system, but becomes restricted to the dorsal foregut and midgut, and associated organs such as dorsal pancreas and stomach. The function of the intronic Gata4 enhancer is dependent upon a conserved Forkhead transcription factor-binding site, which is bound by recombinant FoxA2 in vitro. These studies identify Gata4 as a direct transcriptional target of FoxA2 in the hierarchy of the transcriptional regulatory network that controls the development of the definitive endoderm.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa-CIBERDEM, Sevilla, Spain. anabel.rojas@cabimer.es
authors.forename: Anabel
authors.initials: A
authors.lastname: Rojas
authors.forename: William
authors.initials: W
authors.lastname: Schachterle
authors.forename: Shan-Mei
authors.initials: SM
authors.lastname: Xu
authors.forename: Franz
authors.initials: F
authors.lastname: Martín
authors.forename: Brian L
authors.initials: BL
authors.lastname: Black
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004622:Embryo, Mammalian / Q000378:metabolism; D004707:Endoderm / Q000196:embryology*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism*; D007438:Introns / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
chemical_list: C496503:Foxa2 protein, mouse; D050991:GATA4 Transcription Factor; D051542:Hepatocyte Nuclear Factor 3-beta