title: Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES).
abstract: HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes.
authors.affiliation: Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Gorman
authors.affiliation: Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors.forename: Puja
authors.initials: P
authors.lastname: Singh
authors.affiliation: Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912, USA. Electronic address: ychi@hi.umn.edu.
authors.forename: Young-In
authors.initials: YI
authors.lastname: Chi
mesh_terms: D000818:Animals; D002460:Cell Line; D056970:Co-Repressor Proteins; D005947:Glucose / Q000378:metabolism; D006367:HeLa Cells; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D054730:Protein Interaction Domains and Motifs; D060066:Protein Interaction Maps; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D056970:Co-Repressor Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D007328:Insulin; D012097:Repressor Proteins; C498445:TLE5 protein, human; D005947:Glucose
keywords: AES; Diabetes; Gene regulation; HNF1α; Homeodomain; Insulin secretion; POU transcription factor; Protein–protein interaction