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SUMOylation by the E3 Ligase TbSIZ1/PIAS1 Positively Regulates VSG Expression in


African trypanosomes have evolved one of the most complex strategies of immune evasion by routinely switching the expression of surface proteins called Variant Surface Glycoproteins (VSG), only one of which is expressed at any given time. Previous work has suggested that the recruitment of a single VSG telomeric locus to a discrete nuclear body (ESB) underlies the mechanism responsible for VSG monoallelic expression. Our findings establish unexpected roles for SUMOylation as a specific post-translational modification that marks the ESB and the VSG-ES chromatin. We describe a highly SUMOylated focus (HSF) as a novel nuclear structure that partially colocalizes with the VSG-ES locus and the nuclear body ESB. Furthermore, chromatin SUMOylation is a distinct feature of the active VSG-ES locus, in contrast to other loci investigated. SUMOylation of chromatin-associated proteins is required for efficient recruitment of the polymerase to the VSG-ES promoter and for VSG-ES expression. Altogether, these data suggest the presence of a large number of SUMOylated proteins associated with monoallelic expression as Protein Group SUMOylation. In contrast to the wealth of literature focused on VSG regulation by silencing, our results indicate a positive mechanism via SUMOylation to regulate VSG expression in the infectious form of this protozoan parasite.


Vyšlo v časopise: SUMOylation by the E3 Ligase TbSIZ1/PIAS1 Positively Regulates VSG Expression in. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004545
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004545

Souhrn

African trypanosomes have evolved one of the most complex strategies of immune evasion by routinely switching the expression of surface proteins called Variant Surface Glycoproteins (VSG), only one of which is expressed at any given time. Previous work has suggested that the recruitment of a single VSG telomeric locus to a discrete nuclear body (ESB) underlies the mechanism responsible for VSG monoallelic expression. Our findings establish unexpected roles for SUMOylation as a specific post-translational modification that marks the ESB and the VSG-ES chromatin. We describe a highly SUMOylated focus (HSF) as a novel nuclear structure that partially colocalizes with the VSG-ES locus and the nuclear body ESB. Furthermore, chromatin SUMOylation is a distinct feature of the active VSG-ES locus, in contrast to other loci investigated. SUMOylation of chromatin-associated proteins is required for efficient recruitment of the polymerase to the VSG-ES promoter and for VSG-ES expression. Altogether, these data suggest the presence of a large number of SUMOylated proteins associated with monoallelic expression as Protein Group SUMOylation. In contrast to the wealth of literature focused on VSG regulation by silencing, our results indicate a positive mechanism via SUMOylation to regulate VSG expression in the infectious form of this protozoan parasite.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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