Science and Research

Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis

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.

  • Tschurtschenthaler, M.
  • Kachroo, P.
  • Heinsen, F. A.
  • Adolph, T. E.
  • Ruhlemann, M. C.
  • Klughammer, J.
  • Offner, F. A.
  • Ammerpohl, O.
  • Krueger, F.
  • Smallwood, S.
  • Szymczak, S.
  • Kaser, A.
  • Franke, A.
Publication details
DOI: 10.1038/srep31640
Journal: Scientific reports
Pages: 31640 
Work Type: Original
Location: ARCN
Disease Area: LC
Partner / Member: UKSH (Kiel)
Access-Number: 27538787
See publication on PubMed

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