Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2−/−/Il10−/− Mouse Model
Autor: | Qiyuan Han, Steven R. Tannenbaum, Christopher L. Seiler, Natalia Y. Tretyakova, Thomas J. Y. Kono, James G. Fox, Nicola Parry, Charles G. Knutson |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
colorectal cancer methylome Biology medicine.disease_cause Catalysis lcsh:Chemistry Inorganic Chemistry Transcriptome 03 medical and health sciences 0302 clinical medicine dysplasia inflammatory bowel disease medicine hydroxymethylome Epigenetics Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Spectroscopy Organic Chemistry multi omics analysis and integration hyperplasia Cancer General Medicine medicine.disease biology.organism_classification Computer Science Applications 030104 developmental biology Differentially methylated regions lcsh:Biology (General) lcsh:QD1-999 030220 oncology & carcinogenesis Reduced representation bisulfite sequencing DNA methylation Cancer research Helicobacter hepaticus Carcinogenesis transcriptome |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 364, p 364 (2021) International Journal of Molecular Sciences Volume 22 Issue 1 |
ISSN: | 1422-0067 |
Popis: | Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer. |
Databáze: | OpenAIRE |
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