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| Item Type: | Article |
|---|---|
| Title: | Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine |
| Creators Name: | Herberg, M. and Siebert, S. and Quaas, M. and Thalheim, T. and Rother, K. and Hussong, M. and Altmüller, J. and Kerner, C. and Galle, J. and Schweiger, M.R. and Aust, G. |
| Abstract: | BACKGROUND: Mismatch 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. RESULTS: Histone 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 4 weeks after a single-radiation hit, whereas radiation of Msh2(-/-) mice left their histone methylation profiles almost unchanged. CONCLUSIONS: MMR 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. |
| Keywords: | Intestine, Mismatch Repair Deficiency, Radiation, Msh2, Histone H3 Methylation, Animals, Mice |
| Source: | Clinical Epigenetics |
| ISSN: | 1868-7083 |
| Publisher: | BMC |
| Volume: | 11 |
| Number: | 1 |
| Page Range: | 65 |
| Date: | 27 April 2019 |
| Official Publication: | https://doi.org/10.1186/s13148-019-0639-8 |
| PubMed: | View item in PubMed |
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