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Suppression of methylation-mediated transcriptional gene silencing by ?C1-SAHH protein interaction during geminivirus-betasatellite infection.


ABSTRACT: DNA methylation is a fundamental epigenetic modification that regulates gene expression and represses endogenous transposons and invading DNA viruses. As a counter-defense, the geminiviruses encode proteins that inhibit methylation and transcriptional gene silencing (TGS). Some geminiviruses have acquired a betasatellite called DNA ?. This study presents evidence that suppression of methylation-mediated TGS by the sole betasatellite-encoded protein, ?C1, is crucial to the association of Tomato yellow leaf curl China virus (TYLCCNV) with its betasatellite (TYLCCNB). We show that TYLCCNB complements Beet curly top virus (BCTV) L2? mutants deficient for methylation inhibition and TGS suppression, and that cytosine methylation levels in BCTV and TYLCCNV genomes, as well as the host genome, are substantially reduced by TYLCCNB or ?C1 expression. We also demonstrate that while TYLCCNB or ?C1 expression can reverse TGS, TYLCCNV by itself is ineffective. Thus its AC2/AL2 protein, known to have suppression activity in other geminiviruses, is likely a natural mutant in this respect. A yeast two-hybrid screen of candidate proteins, followed by bimolecular fluorescence complementation analysis, revealed that ?C1 interacts with S-adenosyl homocysteine hydrolase (SAHH), a methyl cycle enzyme required for TGS. We further demonstrate that ?C1 protein inhibits SAHH activity in vitro. That ?C1 and other geminivirus proteins target the methyl cycle suggests that limiting its product, S-adenosyl methionine, may be a common viral strategy for methylation interference. We propose that inhibition of methylation and TGS by ?C1 stabilizes geminivirus/betasatellite complexes.

SUBMITTER: Yang X 

PROVIDER: S-EPMC3197609 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Suppression of methylation-mediated transcriptional gene silencing by βC1-SAHH protein interaction during geminivirus-betasatellite infection.

Yang Xiuling X   Xie Yan Y   Raja Priya P   Li Sizhun S   Wolf Jamie N JN   Shen Qingtang Q   Bisaro David M DM   Zhou Xueping X  

PLoS pathogens 20111020 10


DNA methylation is a fundamental epigenetic modification that regulates gene expression and represses endogenous transposons and invading DNA viruses. As a counter-defense, the geminiviruses encode proteins that inhibit methylation and transcriptional gene silencing (TGS). Some geminiviruses have acquired a betasatellite called DNA β. This study presents evidence that suppression of methylation-mediated TGS by the sole betasatellite-encoded protein, βC1, is crucial to the association of Tomato y  ...[more]

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