title: Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Markus
authors.initials: M
authors.lastname: Tschurtschenthaler
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
authors.forename: Priyadarshini
authors.initials: P
authors.lastname: Kachroo
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
authors.forename: Femke-Anouska
authors.initials: FA
authors.lastname: Heinsen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, CB2 0QQ Cambridge, United Kingdom.
authors.forename: Timon Erik
authors.initials: TE
authors.lastname: Adolph
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
authors.forename: Malte Christoph
authors.initials: MC
authors.lastname: Rühlemann
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
authors.forename: Johanna
authors.initials: J
authors.lastname: Klughammer
authors.affiliation: Department of Pathology, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria.
authors.forename: Felix Albert
authors.initials: FA
authors.lastname: Offner
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.affiliation: Bioinformatics Group, Babraham Institute, CB22 3AT Cambridge, United Kingdom.
authors.forename: Felix
authors.initials: F
authors.lastname: Krueger
authors.affiliation: Epigenetics Programme, Babraham Institute, CB22 3AT Cambridge, United Kingdom.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Smallwood
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, CB2 0QQ Cambridge, United Kingdom.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kaser
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics*; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice