Loss of Msh2 and a single-radiation hit induce common, genome-wide, and persistent epigenetic changes in the intestine.


Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
27 04 2019
Historique:
received: 21 08 2018
accepted: 25 02 2019
entrez: 29 4 2019
pubmed: 29 4 2019
medline: 19 3 2020
Statut: epublish

Résumé

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 Histone H3 methylation increases in Msh2 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.

Sections du résumé

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
RESULTS
Histone H3 methylation increases in Msh2
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.

Identifiants

pubmed: 31029155
doi: 10.1186/s13148-019-0639-8
pii: 10.1186/s13148-019-0639-8
pmc: PMC6486978
doi:

Substances chimiques

Histones 0
MSH2 protein, human EC 3.6.1.3
MutS Homolog 2 Protein EC 3.6.1.3

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

65

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Auteurs

Maria Herberg (M)

Interdisciplinary Center for Bioinformatics (IZBI), Leipzig University, Leipzig, Germany.

Susann Siebert (S)

Laboratory for Translational Epigenetics and Tumor Genetics, University Hospital Cologne, Cologne, Germany.
Graduate School for Biological Sciences (GSfBS), University of Cologne, Cologne, Germany.

Marianne Quaas (M)

Interdisciplinary Center for Bioinformatics (IZBI), Leipzig University, Leipzig, Germany.
Department of Surgery, Research Laboratories, Leipzig University, Liebigstr. 19, D-04103, Leipzig, Germany.

Torsten Thalheim (T)

Interdisciplinary Center for Bioinformatics (IZBI), Leipzig University, Leipzig, Germany.

Karen Rother (K)

Department of Surgery, Research Laboratories, Leipzig University, Liebigstr. 19, D-04103, Leipzig, Germany.
Laboratory for Clinical and Experimental Hepatology (LCEHep) Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.

Michelle Hussong (M)

Laboratory for Translational Epigenetics and Tumor Genetics, University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.

Janine Altmüller (J)

Cologne Center for Genomics, University of Cologne, Cologne, Germany.

Christiane Kerner (C)

Department of Surgery, Research Laboratories, Leipzig University, Liebigstr. 19, D-04103, Leipzig, Germany.

Joerg Galle (J)

Interdisciplinary Center for Bioinformatics (IZBI), Leipzig University, Leipzig, Germany.

Michal R Schweiger (MR)

Laboratory for Translational Epigenetics and Tumor Genetics, University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.

Gabriela Aust (G)

Department of Surgery, Research Laboratories, Leipzig University, Liebigstr. 19, D-04103, Leipzig, Germany. gabriela.aust@medizin.uni-leipzig.de.

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Classifications MeSH