The transcription start site and enhancer landscape of the descending colon in inflammatory bowel disease. Homo sapiens

Inflammatory bowel disease (IBD) is a common and chronic gut disorder, with two subtypes: Crohn's disease (CD) and ulcerative colitis (UC), which are challenging to diagnose. The molecular pathology IBD is not well understood, and the underlying gene regulatory regions have not been comprehensively investigated. Relatedly, most IBD-associated SNPs are located in non-coding regions, and may effect gene regulation. Here, we profiled genome-wide promoter and enhancer activity in the descending colon of IBD patients. IBD-induced enhancer and promoters are highly enriched for IBD-associated SNPs, and can predict IBD diagnosis with an accuracy of 85% in an external cohort. Overall design: This experiment includes a total of 94 patients: 25 patients with active UC(UCa), 17 patients with UC in remission(UCi), 20 patients with active CD(CDa), 3 patients with CD in remission(CDi) and 29 healthy controls (Ctrl).

炎症性肠病（Inflammatory bowel disease, IBD）是一类常见的慢性肠道紊乱疾病，包含克罗恩病（Crohn's disease, CD）与溃疡性结肠炎（ulcerative colitis, UC）两种亚型，临床诊断颇具挑战性。目前对于IBD的分子病理机制尚未充分阐明，其潜在的基因调控区域也未得到全面解析。值得注意的是，绝大多数与IBD相关的单核苷酸多态性（single nucleotide polymorphism, SNP，复数SNPs）均位于非编码区域，可能参与基因调控过程。本研究针对IBD患者的降结肠组织，开展了全基因组范围的启动子与增强子活性谱分析。结果显示，IBD诱导产生的增强子与启动子区域显著富集IBD相关SNPs，且在外部验证队列中可实现85%准确率的IBD诊断预测。实验设计概况：本研究共纳入94名受试者，其中25名为活动性溃疡性结肠炎（UCa）患者、17名为缓解期溃疡性结肠炎（UCi）患者、20名为活动性克罗恩病（CDa）患者、3名为缓解期克罗恩病（CDi）患者，另有29名健康对照（Ctrl）。