Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2-/-/Il10-/- Mouse Model.
Qiyuan HanThomas J Y KonoCharles G KnutsonNicola M ParryChristopher L SeilerJames G FoxSteven R TannenbaumNatalia Y TretyakovaPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- genome wide
- dna methylation
- single cell
- rna seq
- gene expression
- oxidative stress
- papillary thyroid
- mouse model
- poor prognosis
- copy number
- squamous cell
- high glucose
- ulcerative colitis
- genome wide identification
- diabetic rats
- bioinformatics analysis
- binding protein
- endothelial cells
- childhood cancer
- drug induced
- genome wide analysis
- squamous cell carcinoma
- transcription factor
- cell free
- circulating tumor
- long non coding rna