Background How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. Results Specific deletion of Smarcad1 in the mouse intestinal epithelium leads to colitis resistance and substantial changes in gene expression, including a striking increase of expression of several genes linked to innate immunity. Absence of Smarcad1 leads to changes in chromatin accessibility and significant changes in histone H3K9me3 over many sites, including genes that are differentially regulated upon Smarcad1 deletion. We identify candidate members of the gut microbiome that elicit a Smarcad1-dependent colitis response, including members of the poorly understood TM7 phylum. Conclusions Our study sheds light onto the role of the chromatin remodeling machinery in intestinal epithelial cells in the colitis response and shows how a highly conserved chromatin remodeling factor has a distinct role in anti-microbial defense. This work highlights the importance of the intestinal epithelium in the colitis response and the potential of microbial species as pharmacological and probiotic targets in the context of inflammatory diseases.

中文翻译：

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Smarcad1 介导小鼠微生物群诱导的炎症并协调肠上皮细胞中的基因表达

背景 肠上皮细胞如何与微生物群相互作用以及如何在基因表达水平上对其进行调节是关键问题。Smarcad1 是一种保守的染色质重塑因子，其组织功能知之甚少。由于该因子在肠上皮的干细胞和增殖区高度表达，我们探讨了它在该组织中的作用。结果 小鼠肠上皮细胞中 Smarcad1 的特异性缺失导致结肠炎抵抗和基因表达的显着变化，包括与先天免疫相关的几个基因表达的显着增加。Smarcad1 的缺失导致染色质可及性的变化和组蛋白 H3K9me3 在许多位点的显着变化，包括在 Smarcad1 缺失时受到差异调节的基因。我们确定了引起 Smarcad1 依赖性结肠炎反应的肠道微生物组的候选成员，包括知之甚少的 TM7 门成员。结论 我们的研究阐明了染色质重塑机制在肠上皮细胞中在结肠炎反应中的作用，并展示了高度保守的染色质重塑因子如何在抗微生物防御中发挥独特作用。这项工作强调了肠上皮细胞在结肠炎反应中的重要性，以及微生物物种在炎症性疾病背景下作为药理学和益生菌靶标的潜力。结论 我们的研究阐明了染色质重塑机制在肠上皮细胞中在结肠炎反应中的作用，并展示了高度保守的染色质重塑因子如何在抗微生物防御中发挥独特作用。这项工作强调了肠上皮细胞在结肠炎反应中的重要性，以及微生物物种在炎症性疾病背景下作为药理学和益生菌靶标的潜力。结论 我们的研究阐明了染色质重塑机制在肠上皮细胞中在结肠炎反应中的作用，并展示了高度保守的染色质重塑因子如何在抗微生物防御中发挥独特作用。这项工作强调了肠上皮细胞在结肠炎反应中的重要性，以及微生物物种在炎症性疾病背景下作为药理学和益生菌靶标的潜力。