GATA transcription factors as potentiators of gut endoderm differentiation

Gene inactivation studies have shown that members of the GATA family of tra nscription factors are critical for endoderm differentiation in mice, flies and worms, yet how these proteins function in such a conserved development al context has not been understood. We use in vivo footprinting of mouse em bryonic endoderm cells to show that a DNA-binding site for GATA factors is occupied on a liver-specific, transcriptional enhancer of the serum albumin gene. GATA site occupancy occurs in nut endoderm cells at their pluripoten t stage: the cells have the potential to initiate tissue development but th ey have not yet been committed to express albumin or other tissue-specific genes. The GATA-4 isoform accounts for about half of the nuclear GATA-facto r-binding activity in the endoderm. GATA site occupancy persists during hep atic development and is necessary for the activity of albumin gene enhancer . Thus, GATA factors in the endoderm are among the first to bind essential regulatory sites in chromatin. Binding occurs prior to activation of gene e xpression, changes in cell morphology or functional commitment that would i ndicate differentiation. We suggest that GATA factors at target sites in ch romatin may generally help potentiate gene expression and tissue specificat ion in metazoan endoderm development.