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DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis

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  • Hagar Taman
  • Christopher G Fenton
  • Endre Anderssen
  • Jon Florholmen
  • Ruth H Paulssen

Abstract

Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.

Suggested Citation

  • Hagar Taman & Christopher G Fenton & Endre Anderssen & Jon Florholmen & Ruth H Paulssen, 2021. "DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis," PLOS ONE, Public Library of Science, vol. 16(4), pages 1-17, April.
  • Handle: RePEc:plo:pone00:0248905
    DOI: 10.1371/journal.pone.0248905
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