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Profiling of histone 3 lysine 27 acetylation reveals its role in a chronic DSS-induced colitis mouse model.
Molecular Omics ( IF 3.0 ) Pub Date : 2019-08-05 , DOI: 10.1039/c9mo00070d Meng Chen 1 , Qinglan Li , Nan Cao , Yanan Deng , Lianyun Li , Qiu Zhao , Min Wu , Mei Ye
Molecular Omics ( IF 3.0 ) Pub Date : 2019-08-05 , DOI: 10.1039/c9mo00070d Meng Chen 1 , Qinglan Li , Nan Cao , Yanan Deng , Lianyun Li , Qiu Zhao , Min Wu , Mei Ye
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Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. In current dogma, pathogenesis of IBD is attributed to the dysregulated mucosal immune response to gut flora in genetically susceptible individuals, but the genetics evidence from GWAS studies so far is insufficient to explain the observed heritability in IBD. For this discordance, epigenetics has emerged to be one of the important causes. Recent studies have reported that histone acetylation is correlated with the development of IBD, whereas its role and underlying molecular mechanism in the disease still remain elusive. Here, we established a dextran sulfate sodium (DSS)-induced chronic colitis model and performed RNA-sequencing (RNA-seq) and Chromatin Immunoprecipitation followed by NGS sequencing (ChIP-seq) for H3K27ac in the mice colon tissues to investigate whether H3K27ac is involved in the development of intestinal inflammation. We found that the global H3K27ac level and distribution in colon tissue had no significant difference after DSS treatment, while H3K27ac signals were significantly enriched in the typical-enhancers of the DSS group compared with the control. By combining with RNA-seq data (fold change >2), we identified 56 candidate genes as potential target genes for H3K27ac change upon DSS treatment. We further predicted transcription factors (TFs) involved in DSS-induced colitis according to the enhancers with increased H3K27ac. H3K27ac increase in special typical-enhancers in the DSS group is possibly related to the development of intestinal inflammation by up-regulating adjacent gene expression and shifting TF networks, which will provide new insight into the pathogenesis and therapy of IBD.
中文翻译：
对组蛋白3赖氨酸27乙酰化的分析揭示了其在慢性DSS诱导的结肠炎小鼠模型中的作用。
炎症性肠病（IBD）是胃肠道的慢性炎症。在当前的教条中，IBD的发病机理归因于遗传易感人群对肠道菌群的粘膜免疫反应失调，但迄今为止，GWAS研究的遗传学证据不足以解释IBD的遗传性。由于这种矛盾，表观遗传学已经成为重要的原因之一。最近的研究报道，组蛋白乙酰化与IBD的发展有关，而其在疾病中的作用和潜在的分子机制仍然不清楚。这里，我们建立了葡聚糖硫酸钠（DSS）诱导的慢性结肠炎模型，并在小鼠结肠组织中进行了H3K27ac的RNA测序（RNA-seq）和染色质免疫沉淀，然后进行NGS测序（ChIP-seq），以研究H3K27ac是否参与肠道炎症的发展。我们发现，DSS治疗后，全球H3K27ac水平及其在结肠组织中的分布没有显着差异，而与对照组相比，DSS组的典型增强剂中H3K27ac信号显着丰富。通过结合RNA-seq数据（倍数变化> 2），我们确定了56个候选基因作为DSS处理后H3K27ac改变的潜在靶基因。我们根据H3K27ac增加的增强子进一步预测了DSS诱导的结肠炎涉及的转录因子（TFs）。
更新日期：2019-08-05
中文翻译：
对组蛋白3赖氨酸27乙酰化的分析揭示了其在慢性DSS诱导的结肠炎小鼠模型中的作用。
炎症性肠病（IBD）是胃肠道的慢性炎症。在当前的教条中，IBD的发病机理归因于遗传易感人群对肠道菌群的粘膜免疫反应失调，但迄今为止，GWAS研究的遗传学证据不足以解释IBD的遗传性。由于这种矛盾，表观遗传学已经成为重要的原因之一。最近的研究报道，组蛋白乙酰化与IBD的发展有关，而其在疾病中的作用和潜在的分子机制仍然不清楚。这里，我们建立了葡聚糖硫酸钠（DSS）诱导的慢性结肠炎模型，并在小鼠结肠组织中进行了H3K27ac的RNA测序（RNA-seq）和染色质免疫沉淀，然后进行NGS测序（ChIP-seq），以研究H3K27ac是否参与肠道炎症的发展。我们发现，DSS治疗后，全球H3K27ac水平及其在结肠组织中的分布没有显着差异，而与对照组相比，DSS组的典型增强剂中H3K27ac信号显着丰富。通过结合RNA-seq数据（倍数变化> 2），我们确定了56个候选基因作为DSS处理后H3K27ac改变的潜在靶基因。我们根据H3K27ac增加的增强子进一步预测了DSS诱导的结肠炎涉及的转录因子（TFs）。
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