Isoform-specific Intermolecular Disulfide Bond Formation of Heterochromatin Protein 1 (HP1)

Three mammalian isoforms of heterochromatin protein 1 (HP1), alpha, beta, and gamma, 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 HP1 alpha and cysteine 177 in HP1 gamma were involved in intermolecular homodimerization. Although both HP1 alpha and HP1 gamma contain reactive cysteine residues, only HP1 gamma readily and reversibly formed disulfide homodimers under oxidative conditions. Oxidatively dimerized HP1 gamma strongly and transiently interacted with TIF1 beta, a universal transcriptional co-repressor. Under oxidative conditions, HP1 gamma dimerized and held TIF1 beta 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.