Yang Yang, Guan Jingyun, Shaikh Abdul Sami, Liang Yiran, Sun Lichao, Wang Meng, Li Danyang, Qiu Chunhong, Li Xiangzhi
The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Cell and Neurobiology, School of Basic Medicine, Jinan, China.
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Qingdao, China.
Cell Physiol Biochem. 2018;47(5):2159-2169. doi: 10.1159/000491527. Epub 2018 Jul 5.
BACKGROUND/AIMS: Histone acetylation has been demonstrated to be associated with inflammation response. Histone acetyltransferase (HAT) Mof, specifically acetylating lysine 16 of histone H4 (H4K16), has been reported to regulate T cell differentiation. In addition, it has been suggested that acetylation of H4K16 is associated with the inflammatory response. We evaluated the role and potential mechanism of Mof in the development of experimental colitis.
We used Mof conditional knockout mice to study the role of Mof in dextran sulfate sodium (DSS)-induced colitis and detected the differential expression of genes due to Mof deficiency involved in the inflammatory response, particularly the Th17 signaling pathway, by western blotting, quantitative PCR and RNA sequencing (RNA-seq).
A significant elevation of Mof was observed in colonic tissues of mice with DSS-induced colitis. Mof deficiency alleviated the severity of DSS- induced colitis in mice. We found that Th17 signaling pathway associated genes, including Il17a, Il22, RORγt, RORα, Stat3, TGF-β 1, and Il6, were downregulated in colon tissues with Mof deficiency. RNA-seq data analysis suggested that 68 genes were related to inflammatory response processing and 47 genes were downregulated in Mof defective colon tissues.
Our study demonstrated that HAT Mof is involved in the development of colitis, and the lack of Mof ameliorates DSS-induced colitis in mice.
背景/目的：组蛋白乙酰化已被证明与炎症反应相关。据报道，组蛋白乙酰转移酶（HAT）Mof特异性乙酰化组蛋白H4的赖氨酸16（H4K16），可调节T细胞分化。此外，有人提出H4K16的乙酰化与炎症反应有关。我们评估了Mof在实验性结肠炎发展中的作用及潜在机制。
我们使用Mof条件性敲除小鼠研究Mof在葡聚糖硫酸钠（DSS）诱导的结肠炎中的作用，并通过蛋白质印迹、定量PCR和RNA测序（RNA-seq）检测因Mof缺乏导致的参与炎症反应（特别是Th17信号通路）的基因差异表达。
在DSS诱导的结肠炎小鼠的结肠组织中观察到Mof显著升高。Mof缺乏减轻了小鼠DSS诱导的结肠炎的严重程度。我们发现，在Mof缺乏的结肠组织中，与Th17信号通路相关的基因，包括Il17a、Il22、RORγt、RORα、Stat3、TGF-β 1和Il6，均下调。RNA-seq数据分析表明，68个基因与炎症反应过程相关，47个基因在Mof缺陷的结肠组织中下调。
我们的研究表明，HAT Mof参与结肠炎的发展，Mof的缺失可改善小鼠DSS诱导的结肠炎。
