TRYPANOSOMA BRUCEI RAP1: A KEY REGULATOR FOR VSG EXPRESSION

Trypanosoma brucei uses antigenic variation to evade host immune defense. In mammalian host, bloodstream form (BF) T. brucei regularly switches its surface antigen, Variant Surface Glycoprotein (VSG), which is exclusively transcribed from the VSG Expression Sites (ESs) located at the subtelomeric loci. Monoallelic expression of VSG from only one ES ensures the effectiveness of antigenic variation. While in the mid-gut of its insect host, procyclic form (PF) T. brucei expresses procyclins as its surface molecules and all VSGs are silent. VSG expression is therefore dynamically regulated and is essential for T. brucei pathogenesis and normal development. Telomeres are nucleoprotein complexes located at ends of linear chromosomes. They maintain chromosome stability and are essential for genome integrity. In addition, telomeres often form a specialized chromatin structure that influences transcription of genes located nearby. In fact, we have shown recently that tbRAP1, an integral component of the T. brucei telomeric complex, is required for normal subtelomeric VSG silencing in both BF and PF cells. We now have found that depletion of tbRAP1 led to less tightly packed chromatin at the de-repressed ESs compared to silent ones. Furthermore, in bloodstream form cells, tbRAP1 preferentially associates with silent ES marked telomeres but not the active ES marked telomere. Thus it is likely that tbRAP1 acts similarly to its yeast homolog and mediates VSG silencing through modulation of local chromatin structure.