Trypanosoma brucei RAP1 is a key player for VSG silencing

Antigenic variation is a common mechanism to evade the host’s immune defense in several microbial pathogens including Trypanosoma brucei and Plasmodium falciparum. While inside its mammalian host, bloodstream form (BF) T. brucei expresses its surface molecule, Variant Surface Glycoprotein (VSG), exclusively from VSG Expression Sites (ESs) located at subtelomeric loci. Although T. brucei has multiple ESs, only one is fully active at any time, resulting in a single type of VSG being expressed. Monoallelic VSG expression ensures the effectiveness of antigenic variation and maximizes its efficiency. Hence silencing all VSGs except one is essential for T. brucei pathogenesis. While in the mid-gut of its insect host (Tsetse), procyclic form (PF) T. brucei expresses procyclins as surface molecules and all VSGs are silent. Therefore, VSG silencing is also important for normal T. brucei development. VSG silencing depends on several mechanisms, including chromatin remodeling and regulation of transcription elongation. Most importantly, we have recently identified tbRAP1, an intrinsic component of the T. brucei telomere complex, as a key player in silencing ES-linked VSGs in both BF and PF cells. Now we have also found that tbRAP1 appears to preferentially associate with silent ES-marked telomeres, and depletion of tbRAP1 led to a less tightly packed chromatin structure at the derepressed ESs than at the silent ones. Our observations further support the idea that tbRAP1 mediates silencing only at the vicinity where it locates. In addition, it is possible that tbRAP1 acts similarly to its yeast homolog and mediates the subtelomeric silencing through modulation of the chromatin structure.