Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Center for Diabetes & Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.
Endocrinology. 2021 Feb 1;162(2). doi: 10.1210/endocr/bqaa213.
Islet β-cell dysfunction that leads to impaired insulin secretion is a principal source of pathology of diabetes. In type 2 diabetes, this breakdown in β-cell health is associated with compromised islet-enriched transcription factor (TF) activity that disrupts gene expression programs essential for cell function and identity. TF activity is modulated by recruited coregulators that govern activation and/or repression of target gene expression, thereby providing a supporting layer of control. To date, more than 350 coregulators have been discovered that coordinate nucleosome rearrangements, modify histones, and physically bridge general transcriptional machinery to recruited TFs; however, relatively few have been attributed to β-cell function. Here, we will describe recent findings on those coregulators with direct roles in maintaining islet β-cell health and identity and discuss how disruption of coregulator activity is associated with diabetes pathogenesis.
导致胰岛素分泌受损的胰岛 β 细胞功能障碍是糖尿病发病机制的主要来源。在 2 型糖尿病中，这种胰岛 β 细胞功能的衰退与胰岛丰富的转录因子 (TF) 活性受损有关，这会破坏对细胞功能和特性至关重要的基因表达程序。TF 活性受募集的共调节因子调节，这些因子可控制靶基因表达的激活和/或抑制，从而提供支持性的控制层。迄今为止，已经发现了 350 多种共调节因子，它们协调核小体重排、修饰组蛋白，并将一般转录机制物理桥接到募集的 TF 上；然而，与 β 细胞功能相关的相对较少。在这里，我们将描述那些直接参与维持胰岛 β 细胞健康和特性的共调节因子的最新发现，并讨论共调节因子活性的破坏如何与糖尿病发病机制相关。
