Impact of Pdx1-associated chromatin modifiers on islet β-cells.
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.
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
J M
JM
Spaeth
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
E M
EM
Walker
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee. roland.stein@vanderbilt.edu.
R
R
Stein
D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D042421:Histone Code / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D009707:Nucleosomes; D015534:Trans-Activators / Q000235:genetics*
D018398:Homeodomain Proteins; D009707:Nucleosomes; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein
Pdx1; coregulators; diabetes mellitus; islet-enriched transcription factors; type 2 diabetes; β-cell dysfunction