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. Author manuscript; available in PMC: 2016 Jan 27.
Published in final edited form as: Wiley Interdiscip Rev Syst Biol Med. 2015 Jan 27;7(1):1–11. doi: 10.1002/wsbm.1287

Figure 2. Epigenetic regulation in pancreatic endocrine differentiation and maintenance of β-cell function.

Figure 2

The diagram depicts the role of epigenetic regulators as endocrine progenitor cells differentiate into the different endocrine subtypes (1), in regulating cell plasticity (2), and β-cell proliferation (3). (1) Histone deacetylase (HDAC) class I (HDAC-I) and HDAC class IIa (HDAC-IIa) family members have distinct effects on the development of individual endocrine cell types. (2) While genes critical for β-cell function are expressed and marked by H3K4me3 in β-cells, these same genes are silent and bivalently modified in α-cells. This bivalency suggests a plastic epigenetic state for key β-cell genes in α-cells. Additionally, to maintain β-cell identity, genes important for α-cell function have to be actively repressed by the DNA methytransferases DNMT1 and DNMT3a in β-cells. (3) Epigenetic modification of the Cdkn2 locus, encoding a cell cycle inhibitor, by BMI1 and EZH2 promotes β-cell proliferation and regeneration, whereas the methyltransferase MLL1 contributes to β-cell senescence.