The Role of Hepatic Nuclear Factor 1α and PDX-1 in Transcriptional Regulation of the pdx-1 Gene

摘要: The PDX-1 homeodomain transcription factor regulates pancreatic development and adult islet beta cell function. Expression of the pdx-1 gene is almost exclusively localized to cells within endocrine pancreas. Islet cell-selective controlled by evolutionarily conserved subdomain sequences (termed Areas I (-2839 -2520 base pairs (bp)), II (-2252 -2023 bp), III (-1939 -1664 bp)) found 5'-flanking region gene. are independently capable directing reporter activity in transfection assays, with Area I-mediated stimulation dependent upon binding hepatic nuclear 3 (HNF3 beta), a key regulator To identify other transactivators I, highly sequence segments this were mutagenized, their effect on activation was determined. Several sensitive sites data analysis potentially bind endodermally expressed factors, including HNF1 alpha (-2758 -2746 bp, Segment 2), HNF4 (-2742 -2730 4; -2683 -2671 7-8), HNF6 (-2727 -2715 5). alpha, but not HNF6, binds specifically vitro. also shown activate I-driven through 2. In addition, itself stimulate activation. chromatin immunoprecipitation assay performed antisera demonstrated that bound endogenous cells. Our results indicate regulatory factors contribute selective pattern control mediated endodermal regulators like HNF3 beta, PDX-1.