TABLE 3.
Studies exploring DNA methylation responses in patients with Crohn’s disease.
| Study tissue | Sequencing method | Percent CpGs methylated | Global methylation differences | Differential methylation (hyper/hypo methylated) | Genome features impacted | Gene functions enriched at differentially methylated sites | Connection to transcription | |
|---|---|---|---|---|---|---|---|---|
| intestinal mucosa tissue (Li et al., 2021) | Illumina MethylationEPIC (850K) array | NR (not reported) | NR | 5,200 DMPs (2,978/2,222) | The majority of hypermethylated and hypomethylated sites are in the gene bodies | GO analysis showed that differential DNA methylation sites were enriched in the positive regulation of the apoptotic process and the positive regulation of interleukin-8 production in the biological approach. Pathway analysis of differential DNA methylation sites with the KEGG database showed that the differentially expressed sites were mainly concentrated in signal pathways associated with IBD | The differentiated methylated regions directly affected gene expression. (Gene expression dataset downloaded from NCBI GEO datasets | |
| circulating monocytes (CD14 cells) (Li Yim et al., 2020) | HM450 | NR | NR | 15 DMGs (11/4) | Methylation takes place in the promoter region and gene bodies | The STRING database indicates that DMGs do not represent clear functional modules or cellular pathways, but some are implicated in immunological functions | NR | |
| colon specimens (Kim et al., 2020) | HM450 | NR | NR | 3,178 DMPs (2016/1,162) | For hypermethylated regions, 35% were in promoter regions, 35% in the gene body, and 27% in intergenic regions. For hypomethylated areas, 35% in the intergenic region, 32% in the promoter region, and 31% in the gene body | GO analysis reveals several pathways associated with the hypermethylated genes were related to the bleb assembly, regulation of actin filament-based processes, and steroid metabolic processes. Hypomethylated genes are related to leukocyte activation and are involved in immune response, lymphocyte proliferation, and cytokine production | NR | |
| circulating immune cells (Somineni et al., 2019) | WGBS | NR | NR | 1,189 DMPs (976/213) | DMPs are more likely to occur in gene bodies and CpG shelves and less likely in gene promoters and CpG islands and shores | Pathway enrichment analysis revealed pathways relevant to immune function, including tumor necrosis factor-a, JAK-STAT, Ras-related protein 1, and phosphoinositide 3-kinase–Akt signaling, and inflammation, such as the interleukin 17 signaling pathway, cytokine–cytokine receptor interaction, and chemokine signaling | 162 of 585 differentially methylated genes (28%) were differentially expressed. (RNA-Seq). The direction of effects between DNA methylation and gene expression changes in relation to Crohn’s disease appears to be context-dependent, irrespective of the position of the CpG site in the associated gene | |
| peripheral blood mononuclear cells (Ventham et al., 2016) | HM450 (Illumina HumanMethylation450K Beadchip), WGBS | NR | NR | 412 DMPs in Crohn’s Disease with compared to control; four CD-associated DMRs (VMP1, ITGB2, WDR8 and CDC42BPB) | Of the 4 CD-associated DMRs, VMP1 and WDR8 were in gene body, while ITGB-8 was in the 5′-Untranslated region. Most DMPs are located in the gene body | Of all DMPs, 54 significantly enriched GO terms were found, a large proportion of which relate to immune function | Hypermethylation within the TXK gene between the 5′untranslated region and first exon region was associated with reduced TXK expression in CD8+ T cells but no other cell types. Cell specificity plays an important role in methylation and gene expression | |
| purified fibrotic human intestinal fibroblasts (Sadler et al., 2016) | MiGS | NR | NR | 1982 DMRs (1,180/802) | 43.1% of mapped differential DNA methylation occurred within introns, 48.4% occurred within intergenic regions, while only 2.9% occurred within exons, and 2.7% within promoters | Of all the DMRs, the open sea regions (loci greater than 4 kb from CpG islands) contained most of the differential non-CpG island methylation (86.3% and 87.7%) | RNA-seq analysis identified the fibrosis-associated changes in the HIF transcriptome associated with changes in DNA methylation | |
| peripheral blood (Li Yim et al., 2016) | HM450 | NR | NR | 4,287 DMPs (3,338/949) | A statistically significant difference in the DMP distribution for the transcription start sites (TSS1500 and TSS200), the gene body, the first exon, the 3′untranslated region (3′UTR), and the intergenic region were observed |
GO enrichment performances showed enriched processes for immune response, leukocyte activation, and neutrophil chemotaxis | NR | |