Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2020 Dec 31;22(1):364. doi: 10.3390/ijms22010364.
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 -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 , , , and 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.
表观遗传失调被认为在观察到的炎症性肠病（IBD）与结肠肿瘤发展之间的关联中起作用。在本工作中，对源自 IBD 感染的小鼠模型的近端结肠组织进行了 DNA 甲基化组、羟甲基化组和转录组分析。简化代表性亚硫酸氢盐测序（RRBS）和氧化 RRBS（oxRRBS）分析鉴定出 1606 个差异甲基化区域（DMR）和 3011 个差异羟甲基化区域（DhMR）。这些 DMR/DhMR 与与胃肠道疾病、炎症性疾病和癌症相关的基因重叠。RNA-seq 揭示了许多与炎症和癌症相关的基因表达的显著变化。包括 、 、 和 在内的几个基因在 DNA 甲基化/羟甲基化和基因表达水平上均发生变化。总体而言，我们的结果表明，慢性炎症会引发基因组中甲基化和羟甲基化模式的改变，改变关键肿瘤发生基因的表达，并可能有助于结直肠癌的发生。
