Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1 (HP1).
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.
Higo
Shuichiro
S
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Asano
Yoshihiro
Y
Kato
Hisakazu
H
Yamazaki
Satoru
S
Nakano
Atsushi
A
Tsukamoto
Osamu
O
Seguchi
Osamu
O
Asai
Mitsutoshi
M
Asakura
Masanori
M
Asanuma
Hiroshi
H
Sanada
Shoji
S
Minamino
Tetsuo
T
Komuro
Issei
I
Kitakaze
Masafumi
M
Takashima
Seiji
S
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
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