TY - JOUR
T1 - Multi-omics characterization of inflammatory bowel disease-induced hyperplasia/dysplasia in the rag2-/-/il10-/-mouse model
AU - Han, Qiyuan
AU - Kono, Thomas J.Y.
AU - Knutson, Charles G.
AU - Parry, Nicola M.
AU - Seiler, Christopher L.
AU - Fox, James G.
AU - Tannenbaum, Steven R.
AU - Tretyakova, Natalia Y.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - Dysplasia
KW - Hydroxymethylome
KW - Hyperplasia
KW - Inflammatory bowel disease
KW - Methylome
KW - Multi omics analysis and integration
KW - Transcriptome
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U2 - 10.3390/ijms22010364
DO - 10.3390/ijms22010364
M3 - Article
C2 - 33396408
AN - SCOPUS:85099116739
SN - 1661-6596
VL - 22
SP - 1
EP - 21
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 1
M1 - 364
ER -
