Distinct regulation of hepatic nuclear factor 1alpha by NKX6.1 in pancreatic beta cells.

ABSTRACT: Hepatic nuclear factor 1alpha (HNF1alpha) is a key regulator of development and function in pancreatic beta cells and is specifically involved in regulation of glycolysis and glucose-stimulated insulin secretion. Abnormal expression of HNF1alpha leads to development of MODY3 (maturity-onset diabetes of the young 3). We report that NK6 homeodomain 1 (NKX6.1) binds to a cis-regulatory element in the HNF1alpha promoter and is a major regulator of this gene in beta cells. We identified an NKX6.1 recognition sequence in the distal region of the HNF1alpha promoter and demonstrated specific binding of NKX6.1 in beta cells by electrophoretic mobility shift and chromatin immunoprecipitation assays. Site-directed mutagenesis of the NKX6.1 core-binding sequence eliminated NKX6.1-mediated activation a

SUBMITTER: Donelan W 

PROVIDER: S-EPMC2852957 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature