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
Full text not available from this repository.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 | ||||||||||||||||||||||||||||||||||||||||||||||||
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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 | ||||||||||||||||||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/15033 |
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