Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [SI RNA-seq]

Smarcad1 is one of the most conserved chromatin remodelling factors, from yeast to human, with suggested functions in gene silencing, heterochromatin maintenance and genome stability. However, its role in tissue function is poorly understood. As this factor is highly expressed in the stem- and proliferative zone in the intestinal epithelium, we explored the role of this factor in this tissue. Intestine tissue-specific deletion of Smarcad1 resulted in notable changes in gene expression in the small intestine, colon and organoids from small intestine. Strikingly, we found an increase of expression of several genes linked to innate immunity and a dramatic increase of a Bglap3 coding for an osteocalcin isoform, a protein normally expressed in osteoblasts. Our study demonstrates that an innate immunity response can be coordinated by a chromatin remodelling factor Comparisons between wild type mice and Vil-Cre mediated KO of Smarcad1 in the small intestinal epithelium. C57BL/6 background. RNA-seq performed in 4 replicates on whole small intestinal tissue.Smarcad1是从酵母到人类均高度保守的染色质重塑因子（chromatin remodelling factor）之一，既往研究提示其参与基因沉默、异染色质维持及基因组稳定性调控。然而，目前学界对其在组织功能中的作用仍不甚明晰。鉴于该因子在肠上皮的干细胞及增殖区域中呈高表达，我们探究了其在该组织中的功能。肠组织特异性敲除Smarcad1可导致小肠、结肠以及小肠类器官的基因表达发生显著改变。尤为引人注目的是，我们发现多个与先天免疫相关的基因表达上调，且编码骨钙蛋白亚型的Bglap3基因表达大幅升高——该蛋白通常仅在成骨细胞中表达。本研究证实，染色质重塑因子可调控先天免疫应答。本研究以C57BL/6背景的小鼠为模型，对野生型小鼠与小肠上皮中Vil-Cre介导的Smarcad1基因敲除小鼠进行了对比分析。针对完整小肠组织的RNA测序（RNA-seq）共设置4次生物学重复。