GATA-6 - A ZINC-FINGER TRANSCRIPTION FACTOR THAT IS EXPRESSED IN MULTIPLE CELL LINEAGES DERIVED FROM LATERAL MESODERM

Members of the GATA family of zinc finger transcription factors play i mportant roles in the development of several mesodermally derived cell lineages. In the studies described in this report, we have isolated a nd functionally characterized the murine GATA-6 cDNA and protein and d efined the temporal and spatial patterns of GATA-6 gene expression dur ing mammalian development. The GATA-6 and -4 proteins share high-level amino acid sequence identity over a proline-rich region at the amino terminus of the protein that is not conserved in other GATA family mem bers. GATA-6 binds to a functionally important nuclear protein binding site within the cardiac-specific cardiac troponin C (cTnC) transcript ional enhancer. Moreover, the cTnC promoter enhancer can be transactiv ated by overexpression of GATA-6 in noncardiac muscle cells. During ea rly murine embryonic development, the patterns of GATA-6 and -4 gene e xpression are similar, with expression of GATA-6 restricted to the pre cardiac mesoderm, the embryonic heart tube, and the primitive gut. How ever, coincident with the onset of vasculogenesis and development of t he respiratory and urogenital tracts, only the GATA-6 gene is expresse d in arterial smooth muscle cells, the developing bronchi, and the uro genital ridge and bladder. These data are consistent with a model in w hich GATA-6 functions in concert with GATA-4 to direct tissue-specific gene expression during formation of the mammalian heart and gastroint estinal tract, but performs a unique function in programming lineage-r estricted gene expression in the arterial system, the bladder, and the embryonic lung. (C) 1996 Academic Press, Inc.