Open AccessAging is associated with increased chromatin accessibility and reduced polymerase pausing in liver
Author(s) -
Bozukova Mihaela,
Nikopoulou Chrysa,
Kleinenkuhnen Niklas,
Grbavac Dora,
Goetsch Katrin,
Tessarz Peter
Publication year - 2022
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.202211002
Subject(s) - chromatin , biology , rna polymerase ii , transcriptional regulation , transcription (linguistics) , gene expression , regulation of gene expression , rna polymerase , gene , genetics , promoter , microbiology and biotechnology , rna , linguistics , philosophy
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.