THE PIT-1 GENE IS REGULATED BY DISTINCT EARLY AND LATE PITUITARY-SPECIFIC ENHANCERS

The differentiation of three anterior pituitary cell types is regulate d by the tissue-specific POU domain factor Pit-1, which is initially e xpressed on Embryonic Day 13.5-14 in mice. The Pit-1. gene remains con tinuously, highly expressed in the somatotrope, thyrotrope, and lactot rope cells of the adult. Using the Pit-1-defective Snell dwarf as a ge netic background, we demonstrate that the Pit-1 gene utilizes distinct enhancers for initial gene activation and for subsequent autoregulati on (required for maintenance of expression) and that Pit-1-dependent a ctivation of the distal enhancer can be mediated in the absence of the early enhancer. These two distinct enhancers provide the basis for te mporally specific regulation by discrete pituitary-specific factors, e vents likely to be prototypic for regulation of other classes of genes encoding transcription factors controlling terminal differentiation. (C) 1997 Academic Press.