Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_F25E9779430F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver.
Journal
Molecular systems biology
Author(s)
Bozukova M., Nikopoulou C., Kleinenkuhnen N., Grbavac D., Goetsch K., Tessarz P.
ISSN
1744-4292 (Electronic)
ISSN-L
1744-4292
Publication state
Published
Issued date
09/2022
Peer-reviewed
Oui
Volume
18
Number
9
Pages
e11002
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes in the level of transcriptional regulation. Here, we used a multi-omics approach and integrated ATAC-, RNA- and NET-seq to identify age-related changes in the chromatin landscape of murine liver and to investigate how these are linked to transcriptional regulation. We provide the first systematic inventory of the connection between aging, chromatin accessibility, and transcriptional regulation in a whole tissue. Aging in murine liver is characterized by an increase in chromatin accessibility at promoter regions, but not in an increase in transcriptional output. Instead, aging is accompanied by a decrease in promoter-proximal pausing of RNA polymerase II (Pol II), while initiation of transcription is not decreased as assessed by RNA polymerase mapping using CUT&RUN. Based on the data reported, we propose that these age-related changes in transcriptional regulation are due to a reduced stability of the pausing complex.
Keywords
Aging/genetics, Aging/metabolism, Animals, Chromatin/genetics, Chromatin/metabolism, Liver/metabolism, Mice, Promoter Regions, Genetic, RNA Polymerase II/genetics, RNA Polymerase II/metabolism, Transcription, Genetic, aging, chromatin architecture, nascent transcription, promoter-proximal pausing
Pubmed
Web of science
Open Access
Yes
Create date
04/10/2022 12:17
Last modification date
22/01/2024 12:45
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