title: Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1 (HP1).
abstract: Three mammalian isoforms of heterochromatin protein 1 (HP1), α, β, and γ, play diverse roles in gene regulation. Despite their structural similarity, the diverse functions of these isoforms imply that they are additionally regulated by post-translational modifications. Here, we have identified intermolecular disulfide bond formation of HP1 cysteines in an isoform-specific manner. Cysteine 133 in HP1α and cysteine 177 in HP1γ were involved in intermolecular homodimerization. Although both HP1α and HP1γ contain reactive cysteine residues, only HP1γ readily and reversibly formed disulfide homodimers under oxidative conditions. Oxidatively dimerized HP1γ strongly and transiently interacted with TIF1β, a universal transcriptional co-repressor. Under oxidative conditions, HP1γ dimerized and held TIF1β in a chromatin component and inhibited its repression ability. Our results highlight a novel, isoform-specific role for HP1 as a sensor of the cellular redox state.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Higo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Kato
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Seguchi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Asai
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: C000715594:CBX5 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004220:Disulfides; D020033:Protein Isoforms; D012097:Repressor Proteins; D000090266:Chromobox Protein Homolog 5; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28