A Broad m6A Modification Landscape in Inflammatory Bowel Disease.
A Broad m6A Modification Landscape in Inflammatory Bowel Disease.
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炎症性肠病中广泛的 m6A 修饰景观
DOI：
10.3389/fcell.2021.782636
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Nie K;Yi J;Yang Y;Deng M;Yang Y;Wang T;Chen X;Zhang Z;Wang X
背景与目的：n6 -甲基腺苷（N6-Methyladenosine, m6A）是真核生物mRNA上最常见的转录后修饰，影响mRNA的命运。m6A调控在炎症性肠病中的作用尚不清楚。在这里，我们研究了炎症性肠病（IBD）中的m6A结构。方法：从基因表达Omnibus数据库中招募11个人类IBD微阵列数据集，选择4个作为发现队列。来自炎症性肠病多组学数据库的RNA-seq数据集被用作验证队列。在志愿者的结肠样本中测量m6A调节因子。采用一致聚类法和免疫评分法估计IBD中m6A调控的特征。使用7个独立的数据集确定不同亚表型、样本来源和生物治疗反应的m6a相关特征。结果：m6A修饰涉及甲基转移酶（写入器）、去甲基化酶（擦除器）和甲基化读取蛋白（读取器）。m6A调节因子与IBD风险基因之间存在广泛的相互作用。IBD风险位点也可以通过公开m6A测序数据中的m6A修饰进行修饰。此外，m6A调节因子在四个具有共同差异基因（IGF2BP2, HNRNPA2B1， zccchc4和EIF3I）的独立发现队列中表现出广泛的差异表达。在经过验证的队列和入组志愿者的结肠活检样本中，再次确认了差异的m6A调节因子。两簇一致聚类表现出不同的免疫表型。m6a修饰位点存在于核心IBD免疫细胞因子中。另一组IBD数据集揭示了IBD患者临床表型、生物样本和治疗反应亚组之间m6a相关的差异。结论：m6A甲基化调控广泛参与IBD的发生发展。m6A在危险变异体、核心细胞因子、免疫细胞和其他蛋白中的修饰可能会深刻影响病理生理和临床表型。需要进一步的研究来确定其在IBD中的作用。
Background and Aims: N6-Methyladenosine (m6A) is the most common post-transcriptional modification on eukaryotic mRNA, affecting the mRNA’s fate. The role of m6A regulation in inflammatory bowel disease is unclear. Here, we investigated the m6A landscape in inflammatory bowel diseases (IBD). Methods: Eleven human IBD microarray datasets were recruited from the Gene Expression Omnibus database and four were selected as discovery cohorts. An RNA-seq dataset from the Inflammatory Bowel Disease Multi’omics Database was used as a validation cohort. m6A regulators were measured in volunteers’ colonic samples. Consensus clustering and immune scoring were used to estimate the characteristics of m6A regulation in IBD. m6A-related characteristics of different sub-phenotypes, sample sources, and biological therapeutic responses were determined using seven independent datasets. Results: m6A modification involves methyltransferases (writers), demethylases (erasers), and methylation-reading proteins (readers). A wide interaction exists between m6A regulators and IBD risk genes. The IBD risk loci can also be modified by m6A modifications in the public m6A sequencing data. Furthermore, m6A regulators displayed extensive differential expression in four independent discovery cohorts that share common differential genes (IGF2BP2, HNRNPA2B1, ZCCHC4, and EIF3I). In the validated cohort and enrolled volunteers’ colonic biopsy samples, the differential m6A regulators were reconfirmed. Two clusters of consensus clustering exhibit different immune phenotypes. m6A-modified positions exist in the core IBD immune cytokines. Another set of IBD datasets revealed m6A-related differences across clinical phenotypes, biological samples, and therapeutic response subgroups in IBD patients. Conclusion: Regulation of m6A methylation is widely involved in IBD occurrence and development. m6A modifications in risk variants, core cytokines, immune cells, and other proteins may deeply influence the pathophysiology and clinical phenotypes. Further studies are needed to determine its role in IBD.
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DOI：
10.1038/s41575-019-0118-x
发表时间：
2019-05
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Furey TS;Sethupathy P;Sheikh SZ
通讯作者：
Sheikh SZ
急性髓性白血病中致癌 FTO 去甲基酶的小分子靶向
影响因子：
50.3
作者：
Huang, Yue;Su, Rui;Yang, Cai-Guang
通讯作者：
Yang, Cai-Guang
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
7.5
作者：
Han X;Wang L;Han Q
通讯作者：
Han Q
影响因子：
8
作者：
Liang, Guanxiang;Conrad, Maire A.;Bushman, Frederic D.
通讯作者：
Bushman, Frederic D.