Convergence of aging- and rejuvenation-related epigenetic alterations on PRC2 targets [WGBS]

Rejuvenation of tissues in physiologically aging mice can be accomplished by long-term partial reprogramming via expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc). To investigate the epigenetic determinants of partial reprogramming-mediated rejuvenation, we used whole genome bisulfite sequencing to carry out unbiased comprehensive profiling of DNA methylation changes in skin from mice subjected to partial reprogramming, as well as young and untreated old controls. We found a striking convergence of age- and rejuvenation-related epigenetic alterations on targets of the Polycomb repressive complex 2 (PRC2). These results are also supported by a likewise prominent enrichment of PRC2 targets in gene expression data, suggesting that PRC2 activity can modulate aging and mediate tissue rejuvenation. Overall design: WGBS on dorsal skin and isolated tail epidermis samples from five mice treated with long-term partial reprogramming from 15 months of age until 22 months, untreated mice (22 months), and young (3 months) mice.