Clinical Bioinformatics Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT- The Arctic University of Norway, Tromsø, Norway.
Genomics Support Centre Tromsø, Department of Clinical Medicine, Faculty of Health Sciences, UiT- The Arctic University of Norway, Sykehusveien 44, 9037, Tromsø, Norway.
Sci Rep. 2024 Mar 21;14(1):6789. doi: 10.1038/s41598-024-57440-0.
DNA methylation has been implied to play a role in the immune dysfunction associated with inflammatory bowel disease (IBD) and the disease development of ulcerative colitis (UC). Changes of the DNA methylation and correlated gene expression in patient samples with inactive UC might reveal possible regulatory features important for further treatment options for UC. Targeted bisulfite sequencing and whole transcriptome sequencing were performed on mucosal biopsies from patients with active UC (UC, n = 14), inactive UC (RM, n = 20), and non-IBD patients which served as controls (NN, n = 11). The differentially methylated regions (DMRs) were identified by DMRseq. Correlation analysis was performed between DMRs and their nearest differentially expressed genes (DEGs). Principal component analysis (PCA) was performed based on correlated DMR regulated genes. DMR regulated genes then were functional annotated. Cell-type deconvolutions were performed based on methylation levels. The comparisons revealed a total of 38 methylation-regulated genes in inactive UC that are potentially regulated by DMRs (correlation p value < 0.1). Several methylation-regulated genes could be identified in inactive UC participating in IL-10 and cytokine signalling pathways such as IL1B and STAT3. DNA methylation events in inactive UC seem to be fine-tuned by the balancing pro- and anti- inflammatory pathways to maintain a prevailed healing process to restore dynamic epithelium homeostasis.
DNA 甲基化被认为在与炎症性肠病（IBD）相关的免疫功能障碍和溃疡性结肠炎（UC）的疾病发展中发挥作用。在无活性 UC 患者样本中 DNA 甲基化和相关基因表达的变化可能揭示了对 UC 进一步治疗选择可能具有重要意义的调节特征。对活动性 UC（UC，n=14）、无活性 UC（RM，n=20）和非 IBD 患者的粘膜活检进行了靶向亚硫酸氢盐测序和全转录组测序，后者作为对照（NN，n=11）。通过 DMRseq 识别差异甲基化区域（DMR）。对 DMRs 和它们最近的差异表达基因（DEGs）进行相关性分析。基于相关 DMR 调控基因进行主成分分析（PCA）。然后对 DMR 调控基因进行功能注释。基于甲基化水平进行细胞类型去卷积。比较结果显示，无活性 UC 中共有 38 个潜在受 DMR 调控的甲基化调控基因（相关性 p 值<0.1）。在无活性 UC 中可以识别出几个参与 IL-10 和细胞因子信号通路的甲基化调控基因，如 IL1B 和 STAT3。无活性 UC 中的 DNA 甲基化事件似乎通过平衡促炎和抗炎途径进行微调，以维持盛行的愈合过程，恢复动态上皮稳态。
