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A hyper-quiescent chromatin state is a barrier to productive regeneration during aging.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE185708 | GEO | 2023/03/17

REPOSITORIES: GEO

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A hyper-quiescent chromatin state is a barrier to productive regeneration during aging. [DNA-Seq]

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A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Project description:Epigenetic alterations are a key hallmark of aging but have not been extensively explored in tissues. Here, using naturally aged murine liver as a model and extending study 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 old cells show global H3K27me3-driven broad heterochromatinization and transcription suppression. At the local level, site-specific loss of H3K27me3 from promoters of genes encoding developmental transcription factors leads to expression in liver of non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.

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