Fig. 6.

Analysis of human ChIP data reveals activated marks on c-Myc targets in juvenile samples. a H3K4Me3 ChIP-peak distribution across the c-Myc promoter in β cells isolated from a juvenile (5 years) and an adult (48 years) donor. b RNA-seq data demonstrating levels of several c-Myc targets in islets from Ins-c-Myc and control animals. Genes marked in purple show differential H3K4 trimethylation marks in the juvenile donor samples as compared to the adult sample. c H3K4Me3 ChIP-peak distribution in RPL3, IRF9, FKBP4, and SERPINE1 genes in a juvenile (5 years) and adult (48 years) sample. d H3K4Me3 and HeK27Ac marks in the juvenile (5 years and 0.8 years respectively) samples as compared to the adult (48 years and 66 years respectively) samples of c-Myc target genes RCC1 and ODC1. e Schematic representing a key role of c-Myc is the early stages of life, at a time of increased proliferation and immature function within β cells. With age, a reduction in c-Myc occurs concomitant with acquisition of maturation features and loss of replicative capacity. In the Ins-c-Myc animals, β cells continue to express c-Myc well into adulthood and throughout life, leading to a persistence of replicative capacity, and a failure of the cells to undergo maturation, thus leading to dysregulated glucose levels