A hyper-quiescent chromatin state formed during aging is reversed by regeneration.
Mol Cell
; 83(10): 1659-1676.e11, 2023 05 18.
Article
en En
| MEDLINE
| ID: mdl-37116496
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Cromatina
/
Histonas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2023
Tipo del documento:
Article