title: Negative regulation of hypoxic responses via induced Reptin methylation.
abstract: Lysine methylation within histones is crucial for transcriptional regulation and thus links chromatin states to biological outcomes. Although recent studies have extended lysine methylation to nonhistone proteins, underlying molecular mechanisms such as the upstream signaling cascade that induces lysine methylation and downstream target genes modulated by this modification have not been elucidated. Here, we show that Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. Methylated Reptin binds to the promoters of a subset of hypoxia-responsive genes and negatively regulates transcription of these genes to modulate cellular responses to hypoxia.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lee
authors.forename: Yunho
authors.initials: Y
authors.lastname: Kim
authors.forename: Ik Soo
authors.initials: IS
authors.lastname: Kim
authors.forename: Bogyou
authors.initials: B
authors.lastname: Kim
authors.forename: Hee June
authors.initials: HJ
authors.lastname: Choi
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Hi-Jai R
authors.initials: HJ
authors.lastname: Shin
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Olivier
authors.initials: O
authors.lastname: Binda
authors.forename: Or
authors.initials: O
authors.lastname: Gozani
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
authors.forename: Minhyung
authors.initials: M
authors.lastname: Kim
authors.forename: Keun Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics; D002460:Cell Line; D004265:DNA Helicases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006649:Histocompatibility Antigens / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D023041:Xenograft Model Antitumor Assays
chemical_list: D002352:Carrier Proteins; D006649:Histocompatibility Antigens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C525850:TIP49 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human; D008239:Lysine