TY - JOUR T1 - A hyper-quiescent chromatin state formed during aging is reversed by regeneration JF - bioRxiv DO - 10.1101/2023.02.14.528512 SP - 2023.02.14.528512 AU - Na Yang AU - James R. Occean AU - Daniƫl P. Melters AU - Changyou Shi AU - Lin Wang AU - Stephanie Stransky AU - Maire E. Doyle AU - Chang-Yi Cui AU - Michael Delannoy AU - Jinshui Fan AU - Eliza Slama AU - Josephine M. Egan AU - Supriyo De AU - Steven C. Cunningham AU - Rafael de Cabo AU - Simone Sidoli AU - Yamini Dalal AU - Payel Sen Y1 - 2023/01/01 UR - http://biorxiv.org/content/early/2023/02/15/2023.02.14.528512.abstract N2 - Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach, and the first direct visualization of aged chromatin we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcription suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.Competing Interest StatementThe authors have declared no competing interest. ER -