Notch-GATA synergy promotes endoderm-specific expression of ref-1 in C. elegans

The Notch signaling pathway is involved in a wide variety of cell-fate decisions during development. The diverse behavior of Notch-activated cells is thought to depend on tissue- or cell-type-specific transcription factors, yet the identities of such factors and the mechanism of cooperation with the Notch pathway are largely unknown. We identify here an enhancer in the promoter of ref-1, a C. elegans Notch target, which promotes Notch-dependent expression in mesodermal and endodermal cells. The enhancer contains predicted binding sites for the Notch transcriptional effector LAG-1/CSL that are essential for expression, a non-CSL site required for mesodermal expression, and four predicted binding sites for GATA transcription factors that are required for endodermal expression. We show that endodermal expression involves the GATA transcription factor ELT-2, and that ELT-2 can bind LAG-1/CSL in vitro. In many types of Notch-activated embryonic cells, ectopic ELT-2 is sufficient to drive expression of reporters containing the enhancer.