The proinflammatory cytokine TNF induces DNA demethylation-dependent and -independent activation of interleukin-32 expression

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	The proinflammatory cytokine TNF induces DNA demethylation-dependent and -independent activation of interleukin-32 expression
	Zhao, Zuodong ; Lan, Mengying ; Li, Jingjing ; Dong, Qiang ; Li, Xiang ; Liu, Baodong ; Li, Gang ; Wang, Hailin ; Zhang, Zhuqiang ; Zhu, Bing
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2019-04-26
卷号	294 期号:17 页码:6785-6795
关键词	DNA methylation DNA demethylation tumor necrosis factor (TNF) gene regulation NF-B inflammation epigenetics transcription gene activation IL-32 TNF
ISSN号	0021-9258
英文摘要	IL-32 is a cytokine involved in proinflammatory immune responses to bacterial and viral infections. However, the role of epigenetic events in the regulation of IL-32 gene expression is understudied. Here we show that IL-32 is repressed by DNA methylation in HEK293 cells. Using ChIP sequencing, locus-specific methylation analysis, CRISPR/Cas9-mediated genome editing, and RT-qPCR (quantitative RT-PCR) and immunoblot assays, we found that short-term treatment (a few hours) with the proinflammatory cytokine tumor necrosis factor (TNF) activates IL-32 in a DNA demethylation-independent manner. In contrast, prolonged TNF treatment (several days) induced DNA demethylation at the promoter and a CpG island in the IL-32 gene in a TET (ten-eleven translocation) family enzyme- and NF-B-dependent manner. Notably, the hypomethylation status of transcriptional regulatory elements in IL-32 was maintained for a long time (several weeks), causing elevated IL-32 expression even in the absence of TNF. Considering that IL-32 can, in turn, induce TNF expression, we speculate that such feedforward events may contribute to the transition from an acute inflammatory response to chronic inflammation.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/43040]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
作者单位	1.Tsinghua Univ, Sch Life Sci, Tsinghua Univ Peking Univ Natl Inst Biol Sci Join, Beijing 100084, Peoples R China 2.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 3.Nat Inst Biol Sci, Beijing 102206, Peoples R China 4.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 5.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Zuodong,Lan, Mengying,Li, Jingjing,et al. The proinflammatory cytokine TNF induces DNA demethylation-dependent and -independent activation of interleukin-32 expression[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(17):6785-6795.
APA	Zhao, Zuodong.,Lan, Mengying.,Li, Jingjing.,Dong, Qiang.,Li, Xiang.,...&Zhu, Bing.(2019).The proinflammatory cytokine TNF induces DNA demethylation-dependent and -independent activation of interleukin-32 expression.JOURNAL OF BIOLOGICAL CHEMISTRY,294(17),6785-6795.
MLA	Zhao, Zuodong,et al."The proinflammatory cytokine TNF induces DNA demethylation-dependent and -independent activation of interleukin-32 expression".JOURNAL OF BIOLOGICAL CHEMISTRY 294.17(2019):6785-6795.