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Sci Rep. 2016 Aug 19;6:31640. doi: 10.1038/srep31640.

Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis.

Author information

Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, CB2 0QQ Cambridge, United Kingdom.
Department of Medicine II (Gastroenterology &Hepatology), Medical University Innsbruck, 6020 Innsbruck, Austria.
Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
Department of Pathology, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria.
Institute of Human Genetics, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
Bioinformatics Group, Babraham Institute, CB22 3AT Cambridge, United Kingdom.
Epigenetics Programme, Babraham Institute, CB22 3AT Cambridge, United Kingdom.


Inflammatory bowel disease (IBD) arises by unknown environmental triggers in genetically susceptible individuals. Epigenetic regulation of gene expression may integrate internal and external influences and may thereby modulate disease susceptibility. Epigenetic modification may also affect the germ-line and in certain contexts can be inherited to offspring. This study investigates epigenetic alterations consequent to experimental murine colitis induced by dextran sodium sulphate (DSS), and their paternal transmission to offspring. Genome-wide methylome- and transcriptome-profiling of intestinal epithelial cells (IECs) and sperm cells of males of the F0 generation, which received either DSS and consequently developed colitis (F0(DSS)), or non-supplemented tap water (F0(Ctrl)) and hence remained healthy, and of their F1 offspring was performed using reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), respectively. Offspring of F0(DSS) males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0(DSS) mice was associated with decreased body weight at baseline of their F1 offspring, and these F1 mice exhibited increased susceptibility to DSS-induced colitis compared to offspring from F0(Ctrl) males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis.

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