Department of Genetics and Institute of Diabetes, Obesity & Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Semin Cell Dev Biol. 2012 Aug;23(6):693-700. doi: 10.1016/j.semcdb.2012.06.002. Epub 2012 Jun 21.
Multiple signaling systems and transcription factor cascades control pancreas development and endocrine cell fate determination. Epigenetic processes contribute to the control of this transcriptional hierarchy, involving both histone modifications and DNA methylation. Here, we summarize recent advances in the field that demonstrate the importance of epigenetic regulation in pancreas development, β-cell proliferation, and cell fate choice. These breakthroughs were made using the phenotypic analysis of mice with mutations in genes that encode histone modifying enzymes and related proteins; by application of activators or inhibitors of the enzymes that acetylate or methylate histones to fetal pancreatic explants in culture; and by genomic approaches that determined the patterns of histone modifications and chromatin state genome-wide.
多种信号系统和转录因子级联控制着胰腺的发育和内分泌细胞命运的决定。表观遗传过程有助于控制这种转录层次结构，包括组蛋白修饰和 DNA 甲基化。在这里，我们总结了该领域的最新进展，这些进展表明了表观遗传调控在胰腺发育、β 细胞增殖和细胞命运选择中的重要性。这些突破是通过对编码组蛋白修饰酶和相关蛋白的基因突变小鼠进行表型分析、在培养的胎胰腺外植体中应用乙酰化或甲基化组蛋白的酶的激活剂或抑制剂、以及通过确定组蛋白修饰和染色质状态的全基因组模式的基因组方法来实现的。
