Impact of Pdx1-associated chromatin modifiers on islet β-cells

Diabetes Obes Metab. 2016 Sep;18 Suppl 1(Suppl 1):123-7. doi: 10.1111/dom.12730.

Abstract

Diabetes mellitus arises from insufficient insulin secretion from pancreatic islet β-cells. In type 2 diabetes (T2D), β-cell dysfunction is associated with inactivation and/or loss of transcription factor (TF) activity, including Pdx1. Notably, this particular TF is viewed as a master regulator of pancreas development and islet β-cell formation, identity and function. TFs, like Pdx1, recruit coregulators to transduce activating and/or repressing signals to the general transcriptional machinery for controlling gene expression, including modifiers of DNA, histones and nucleosome architecture. These coregulators impart a secondary layer of control that can be exploited to modulate TF activity. In this review, we describe Pdx1-recruited coregulators that impact chromatin structure, consequently influencing normal β-cell function and likely Pdx1 activity in pathophysiological settings.

Keywords: Pdx1; coregulators; diabetes mellitus; islet-enriched transcription factors; type 2 diabetes; β-cell dysfunction.

Publication types

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

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly / genetics*
  • DNA Methylation / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Gene Expression Regulation / genetics*
  • Histone Code / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Nucleosomes
  • Trans-Activators / genetics*

Substances

  • Homeodomain Proteins
  • Nucleosomes
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein