Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes.

Molecular Microbiology
Qiao-Ping WangDavid Horn

Abstract

African trypanosomes evade the host immune response through antigenic variation, which is achieved by periodically expressing different variant surface glycoproteins (VSGs). VSG expression is monoallelic such that only one of approximately 15 telomeric VSG expression sites (ESs) is transcribed at a time. Epigenetic regulation is involved in VSG control but our understanding of the mechanisms involved remains incomplete. Histone deacetylases are potential drug targets for diseases caused by protozoan parasites. Here, using recombinant expression we show that the essential Trypanosoma brucei deacetylases, DAC1 (class I) and DAC3 (class II) display histone deacetylase activity. Both DAC1 and DAC3 are nuclear proteins in the bloodstream stage parasite, while only DAC3 remains concentrated in the nucleus in insect-stage cells. Consistent with developmentally regulated localization, DAC1 antagonizes SIR2rp1-dependent telomeric silencing only in the bloodstream form, indicating a conserved role in the control of silent chromatin domains. In contrast, DAC3 is specifically required for silencing at VSG ES promoters in both bloodstream and insect-stage cells. We conclude that DAC1 and DAC3 play distinct roles in subtelomeric gene silenci...Continue Reading

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Citations

May 30, 2012·Expert Reviews in Molecular Medicine·Sam AlsfordMark C Field
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Nov 2, 2021·Frontiers in Cell and Developmental Biology·Naiwen ZhangQijun Chen

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Methods Mentioned

BETA
acetylation
PCR
histone acetylation
transfection
flow cytometry
protein assay

Software Mentioned

Metamorph
Photoshop Elements

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