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A hyper-quiescent chromatin state formed during aging is reversed by regeneration.
- Source :
-
Molecular cell [Mol Cell] 2023 May 18; Vol. 83 (10), pp. 1659-1676.e11. Date of Electronic Publication: 2023 Apr 27. - Publication Year :
- 2023
-
Abstract
- 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 transcriptional 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.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Published by Elsevier Inc.)
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 83
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 37116496
- Full Text :
- https://doi.org/10.1016/j.molcel.2023.04.005