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	Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation
	Liu, Xing1,2; Chen, Zhu2,3; Xu, Chenxi1,2; Leng, Xiaoqian1,2; Cao, Hong1,2; Ouyang, Gang2; Xiao, Wuhan1,2
刊名	NUCLEIC ACIDS RESEARCH
	2015-05-26
卷号	43期号:10页码:5081-5098
ISSN号	0305-1048
通讯作者	Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China.
英文摘要	Hypoxia-inducible factor (HIF)-1 alpha and HIF-2 alpha are the main regulators of cellular responses to hypoxia. Post-translational modifications of HIF-1 alpha and 2 alpha are necessary to modulate their functions. The methylation of non-histone proteins by Set7, an SET domain-containing lysine methyltransferase, is a novel regulatory mechanism to control cell protein function in response to various cellular stresses. In this study, we show that Set7 methylates HIF-1 alpha at lysine 32 and HIF-2 alpha at lysine K29; this methylation inhibits the expression of HIF-1 alpha/2 alpha targets by impairing the occupancy of HIF-alpha on hypoxia response element of HIF target gene promoter. Set7-null fibroblasts and the cells with shRNA-knocked down Set7 exhibit upregulated HIF target genes. Set7 inhibitor blocks HIF-1 alpha/2 alpha methylation to enhance HIF target gene expression. Set7-null fibroblasts and the cells with shRNA-knocked down Set7 or inhibition of Set7 by the inhibitor subjected to hypoxia display an increased glucose uptake and intracellular adenosine triphosphate levels. These findings define a novel modification of HIF-1 alpha/2 alpha and demonstrate that Set7-medited lysine methylation negatively regulates HIF-alpha transcriptional activity and HIF-1 alpha-mediated glucose homeostasis.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemistry & Molecular Biology
研究领域[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TUMOR-SUPPRESSOR PROTEIN ; INDUCED CELL-DEATH ; LYSINE METHYLATION ; TRANSCRIPTIONAL ACTIVITY ; SET9-MEDIATED METHYLATION ; PHOSPHORYLATION SWITCH ; STABILIZES HIF-1-ALPHA ; HISTONE DEMETHYLASES ; NONHISTONE PROTEINS ; GLUCOSE-METABOLISM
收录类别	SCI
语种	英语
WOS记录号	WOS:000355929200029
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/23970]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 2.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China 3.Maternal & Child Hlth Hosp Hubei Prov, Dept Reprod, Wuhan, Peoples R China
推荐引用方式 GB/T 7714	Liu, Xing,Chen, Zhu,Xu, Chenxi,et al. Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation[J]. NUCLEIC ACIDS RESEARCH,2015,43(10):5081-5098.
APA	Liu, Xing.,Chen, Zhu.,Xu, Chenxi.,Leng, Xiaoqian.,Cao, Hong.,...&Xiao, Wuhan.(2015).Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation.NUCLEIC ACIDS RESEARCH,43(10),5081-5098.
MLA	Liu, Xing,et al."Repression of hypoxia-inducible factor alpha signaling by Set7-mediated methylation".NUCLEIC ACIDS RESEARCH 43.10(2015):5081-5098.

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