Spaeth J M, Walker E M, Stein R
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
Diabetes Obes Metab. 2016 Sep;18 Suppl 1(Suppl 1):123-7. doi: 10.1111/dom.12730.
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.
糖尿病源于胰岛β细胞分泌胰岛素不足。在2型糖尿病（T2D）中，β细胞功能障碍与转录因子（TF）活性的失活和/或丧失有关，包括胰腺十二指肠同源盒1（Pdx1）。值得注意的是，这种特定的转录因子被视为胰腺发育和胰岛β细胞形成、特性及功能的主要调节因子。转录因子，如Pdx1，招募共调节因子，将激活和/或抑制信号传递给通用转录机制以控制基因表达，包括DNA、组蛋白和核小体结构的修饰因子。这些共调节因子赋予了第二层控制，可用于调节转录因子活性。在本综述中，我们描述了影响染色质结构的Pdx1招募的共调节因子，从而影响正常β细胞功能以及病理生理环境中可能的Pdx1活性。
