Universität zu Köln

Bozukova, Mihaela, Nikopoulou, Chrysa ORCID: 0000-0001-7982-7737, Kleinenkuhnen, Niklas, Grbavac, Dora, Goetsch, Katrin and Tessarz, Peter ORCID: 0000-0002-6953-9835 (2022). Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver. Mol. Syst. Biol., 18 (9). HOBOKEN: WILEY. ISSN 1744-4292

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bozukova, Mihaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikopoulou, Chrysa UNSPECIFIED orcid.org/0000-0001-7982-7737 UNSPECIFIED Kleinenkuhnen, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Grbavac, Dora UNSPECIFIED UNSPECIFIED UNSPECIFIED Goetsch, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Tessarz, Peter UNSPECIFIED orcid.org/0000-0002-6953-9835 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-671492
DOI:	10.15252/msb.202211002
Journal or Publication Title:	Mol. Syst. Biol.
Volume:	18
Number:	9
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1744-4292
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RNA-POLYMERASE; TRANSCRIPTION; PROMOTER; REVEALS; COMPLEX; DISTINCT; PACKAGE; NELF; DSIF; SEQ Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67149