Epigenetic regulation of pancreas development and function.

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.