Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES)

Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):14-20. doi: 10.1016/j.bbrc.2015.11.007. Epub 2015 Nov 6.

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.

Keywords: AES; Diabetes; Gene regulation; HNF1α; Homeodomain; Insulin secretion; POU transcription factor; Protein–protein interaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Co-Repressor Proteins
  • Glucose / metabolism
  • HeLa Cells
  • Hepatocyte Nuclear Factor 1-alpha / chemistry
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism*
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Mutation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Maps
  • Repressor Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Co-Repressor Proteins
  • Hepatocyte Nuclear Factor 1-alpha
  • Insulin
  • Repressor Proteins
  • TLE5 protein, human
  • Glucose