title: Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK4A locus.
abstract: Activation of Raf reduces the repressive histone mark H3K27me3 at the INK4a locus by inducing the H3K27me3 demethylase JMJD3. During hypoxia, the catalyitc activity of JMJD3 is reduced due to the limited availability of O2as a substrate. In our study, we found that hypoxia prevented Raf-induced JMJD3 from demethylating H3K27me3 at the INK4a locus. Nonetheless, hypoxia did not prevent Raf signaling from inducing INK4a mRNA. Interestingly, we found that hypoxia strongly enhanced the active histone mark H3K4me3 at the INK4a locus by inhibiting the H3K4me3 demethylases JARID1A and JARID1B. Therefore, this study demonstrates that the O2concentration in the microenvironment differentially affects the repressive methylation on K27 and the activating methylation on K4 at the INK4a locus by inhibiting the H3K27me3 and H3K4me3 demethylases.
authors.affiliation: Department of Life Science, University of Seoul, Korea.
authors.forename: Soojeong
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Life Science, University of Seoul, Korea.
authors.forename: Bongju
authors.initials: B
authors.lastname: Park
authors.affiliation: Department of Life Science, University of Seoul, Korea.
authors.forename: Kang
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Life Science, University of Seoul, Korea.
authors.forename: Yunwon
authors.initials: Y
authors.lastname: Moon
authors.affiliation: Department of Life Science, University of Seoul, Korea.
authors.forename: Ho-Youl
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Life Science, University of Seoul, Korea. hspark@uos.ac.kr.
authors.forename: Hyunsung
authors.initials: H
authors.lastname: Park
mesh_terms: D000107:Acetylation; D015687:Cell Hypoxia; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D056485:Retinoblastoma-Binding Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D006657:Histones; D009687:Nuclear Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C070050:KDM5A protein, human; C119611:KDM5B protein, human; D056485:Retinoblastoma-Binding Protein 2; D010100:Oxygen
keywords: Hypoxia; INK4A locus; JMJD3