Universität zu Köln

Herberg, Maria, Siebert, Susann, Quaas, Marianne, Thalheim, Torsten, Rother, Karen, Hussong, Michelle, Altmueller, Janine, Kerner, Christiane, Galle, Joerg, Schweiger, Michal R. and Aust, Gabriela (2019). Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine. Clin. Epigenetics, 11. LONDON: BMC. ISSN 1868-7083

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Abstract

BackgroundMismatch repair (MMR)-deficiency increases the risk of colorectal tumorigenesis. To determine whether the tumors develop on a normal or disturbed epigenetic background and how radiation affects this, we quantified genome-wide histone H3 methylation profiles in macroscopic normal intestinal tissue of young radiated and untreated MMR-deficient VCMsh2(LoxP/LoxP) (Msh2(-/-)) mice months before tumor onset.ResultsHistone H3 methylation increases in Msh2(-/-) compared to control Msh2(+/+) mice. Activating H3K4me3 and H3K36me3 histone marks frequently accumulate at genes that are H3K27me3 or H3K4me3 modified in Msh2(+/+) mice, respectively. The genes recruiting H3K36me3 enrich in gene sets associated with DNA repair, RNA processing, and ribosome biogenesis that become transcriptionally upregulated in the developing tumors. A similar epigenetic effect is present in Msh2(+/+) mice 4weeks after a single-radiation hit, whereas radiation of Msh2(-/-) mice left their histone methylation profiles almost unchanged.ConclusionsMMR deficiency results in genome-wide changes in histone H3 methylation profiles preceding tumor development. Similar changes constitute a persistent epigenetic signature of radiation-induced DNA damage.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Herberg, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Siebert, Susann UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Marianne UNSPECIFIED UNSPECIFIED UNSPECIFIED Thalheim, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Rother, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hussong, Michelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerner, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Galle, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweiger, Michal R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aust, Gabriela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-150330
DOI:	10.1186/s13148-019-0639-8
Journal or Publication Title:	Clin. Epigenetics
Volume:	11
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1868-7083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA MISMATCH REPAIR; STEM-CELLS; HISTONE MODIFICATIONS; GENE ONTOLOGY; MOUSE; METHYLATION; DEFICIENCY; PHOSPHORYLATION; PATHWAYS; CANCER Multiple languages Oncology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15033