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Genome-Wide DNA Methylation in Treatment-Naïve Ulcerative Colitis

Permanent lenke
https://hdl.handle.net/10037/14020
DOI
https://doi.org/10.1093/ecco-jcc/jjy117
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article.pdf (288.7Kb)
Publisher's version (PDF)
Dato
2018-08-22
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Taman, Hagar; Fenton, Christopher Graham; Hensel, Inga Viktoria; Anderssen, Endre; Florholmen, Jon; Paulssen, Ruth H
Sammendrag

Background and Aims: The aim of this study was to investigate the genome-wide DNA methylation status in treatment-naïve ulcerative colitis [UC], and to explore the relationship between DNA methylation patterns and gene expression levels in tissue biopsies from a well-stratified treatment-naïve UC patient group.

Methods; Mucosal biopsies from treatment-naïve patients [n = 10], and a healthy control group [n = 11] underwent genome-wide DNA bisulfite sequencing. Principal component analysis [PCA] and diverse statistical methods were applied to obtain a dataset of differentially methylated genes. DNA methylation annotation was investigated using the UCSC Genome Browser. Gene set enrichments were obtained using the Kyoto Encyclopaedia of Genes and Genomes [KEGG] and PANTHER.

Results: Of all significantly differentially expressed genes [DEGs], 25% correlated with DNA methylation patterns; 30% of these genes were methylated at CpG sites near their transcription start site [TSS]. Hyper-methylation was observed for genes involved in homeostasis and defence, whereas hypo-methylation was observed for genes playing a role in immune response [i.e. chemokines and interleukins]. Of the differentially DNA methylated genes, 25 were identified as inflammatory bowel disease [IBD] susceptibility genes. Four genes [DEFFA6, REG1B, BTNL3, OLFM4] showed DNA methylation in the absence of known CpG islands.

Conclusions: Genome-wide DNA methylation analysis revealed distinctive functional patterns for hyper-and hypo-methylation in treatment-naïve UC. These distinct patterns could be of importance in the development and pathogenesis of UC. Further investigation of DNA methylation patterns may be useful in the development of the targeting of epigenetic processes, and may allow new treatment and target strategies for UC patients.

Er en del av
Taman, H. (2022). Epigenetics in Inflammatory Bowel Disease. Contribution of DNA methylation to Ulcerative Colitis pathogenesis. (Doctoral thesis). https://hdl.handle.net/10037/24490.
Forlag
Oxford University Press (OUP)
Sitering
Taman, H., Fenton, C.G., Hensel, I.V., Anderssen, E., Florholmen, J. & Paulssen, R.H. (2018). Genome-Wide DNA Methylation in Treatment-Naïve Ulcerative Colitis. Journal of Crohn's and Colitis. https://doi.org/10.1093/ecco-jcc/jjy117
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