Back to Search
Start Over
Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine
- Source :
- Clinical Epigenetics, Vol 11, Iss 1, Pp 1-12 (2019)
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 18687075 and 18687083
- Volume :
- 11
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Clinical Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f3652322832b4382953c498b1a202463
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13148-019-0639-8