Universität zu Köln

Bozukova, Mihaela (2022). Aging alters chromatin accessibility and transcriptional regulation in murine liver tissue. PhD thesis, Universität zu Köln.

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Abstract

Regulation of gene expression is tightly linked to the organization of the mammalian genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in gene expression profiles. However, little is known about the detailed changes in transcriptional regulation with age. Here, we systematically characterize age-related changes in the local chromatin landscape of murine liver tissue and their link to transcriptional regulation. To the best of our knowledge, this is the first systematic inventory of the connection between aging, chromatin accessibility and transcriptional regulation in vivo, in a whole tissue. We observe that aging of murine liver tissue is accompanied by an increase in chromatin accessibility at promoter regions of protein-coding genes. Yet, although promoter accessibility is a requirement for transcription, the increased accessibility did not result in enhanced transcriptional output. Instead, aging is accompanied by a decrease of promoter-proximal pausing of RNA polymerase II (Pol II). We propose that these changes in transcriptional regulation are due to a reduced stability of the pausing complex and may represent a mechanism to compensate for the age-related increase in chromatin accessibility in order to prevent aberrant transcription.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Bozukova, Mihaela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-635563
Date:	2022
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Außeruniversitäre Forschungseinrichtungen > MPI for Biology of Ageing
Subjects:	Natural sciences and mathematics
Uncontrolled Keywords:	Keywords Language chromatin UNSPECIFIED epigenetics UNSPECIFIED transcription UNSPECIFIED aging UNSPECIFIED polymerase pausing UNSPECIFIED
Date of oral exam:	8 December 2021
Referee:	Name Academic Title Tessarz, Peter Dr Beyer, Andreas Dr
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/63556