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

Bozukova, M., Nikopoulou, C., Kleinenkuhnen, N., Grbavac, D., Goetsch, K., & Tessarz, P. (2022). Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver. Mol Syst Biol, 18(9), e11002. doi:10.15252/msb.202211002.

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Bozukova, M.1, Author           
Nikopoulou, C.1, Author           
Kleinenkuhnen, N.1, Author           
Grbavac, D.1, Author           
Goetsch, K.1, Author           
Tessarz, P.1, Author           
Affiliations:
1Tessarz – Chromatin and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942296              

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Free keywords: *Aging/genetics/metabolism Animals *Chromatin/genetics/metabolism Liver/metabolism Mice Promoter Regions, Genetic *RNA Polymerase II/genetics/metabolism Transcription, Genetic aging chromatin architecture nascent transcription promoter-proximal pausing
 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.

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 Dates: 2022-09-012022
 Publication Status: Issued
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 Identifiers: Other: 36082605
DOI: 10.15252/msb.202211002
ISSN: 1744-4292 (Electronic)1744-4292 (Linking)
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Title: Mol Syst Biol
Source Genre: Journal
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Pages: - Volume / Issue: 18 (9) Sequence Number: - Start / End Page: e11002 Identifier: -