title: Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α.
abstract: Lysine (K)-specific demethylase 6B (KDM6B) is a histone H3K27 demethylase, which specifically catalyzes the demethylation of H3 lysine-27 tri/dimethylation (H3K27me3/2). KDM6B can activate gene transcription by promoting transcriptional elongation which is associated with RNA polymerase II and related elongation factors. So KDM6B is important for the regulation of gene expression. Previous studies have indicated that several histone demethylases such as KDM3A, KDM4B, and KDM4C are regulated by hypoxia-inducible factor (HIF). But, the effect of hypoxia on KDM6B is not fully understood. In this study, we found that the expression levels of KDM6B mRNA and protein are modestly up-regulated under hypoxia (1% O2) or mimic hypoxia (desferrioxamine mesylate or CoCl2 treatment) (P<0.05). The result of RNAi shows that the up-regulation of KDM6B is dependent on HIF-2α, but not on HIF-1α. The result of chromatin immunoprecipitation assay indicates that there is a hypoxia response element in KDM6B promoter (-4041 to -4037). The result of Co-IP assay indicates that KDM6B can form complex with HIF-2α or HIF-1α. The knockdown experiment implies that KDM6B is a potential regulator for HIF-2α target genes. These data demonstrate that KDM6B is a new hypoxia response gene regulated by HIF-2α. Our results also show that KDM6B is a potential co-activator of HIF-α, which is important for the activation of hypoxia response genes.
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Zhantao
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors.forename: Xuliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Pan
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
authors.forename: Weiren
authors.initials: W
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen 518036, China.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China caizhiming2000@163.com xlduan0311@163.com.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China caizhiming2000@163.com xlduan0311@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
mesh_terms: D021581:Active Transport, Cell Nucleus; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002384:Catalysis; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction; D015533:Transcriptional Activation; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1; C524220:KDM6B protein, human
keywords: H3K27 demethylase; KDM6B; histone; hypoxia; hypoxia-inducible factor-2α