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

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 activity, including Pdx1. Notably, this particular transcription factor is viewed as a master regulator of pancreas development and islet β-cell formation, identity and function. Transcription factors, 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 transcription factor 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.