Latest work on histone chaperones and VSG ES regulation published in Nucleic Acids Research.

Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei. Nucleic Acids Res. (PubMed | PDF)

A longstanding mystery in T. brucei biology is how these parasites are able to express a single variant surface glycoprotein (VSG) from a single sub-telomeric expression site (ES), while repressing at least 14 others. While we cannot claim to have solved this mystery, we have added weight to the contention that chromatin is a key, though probably not the only, player in this process.

We’ve demonstrated that the histone chaperones, CAF-1b and ASF1A, contribute to the maintenance of silent VSG ESs in T. brucei. RNAi depletion of either of these histone chaperones leads to de-repression of the ES promoter, in a cell cycle dependent manner; ASF1A loss led to ES promoter de-repression throughout the cell cycle, while CAF-1b loss resulted in greater de-repression in S and G2/M phases, due to nucleosome depletion. As has been reported for other factors involved in ES silencing, we didn’t see any significant readthrough to the ~50kb distal VSG gene following chaperone depletion; indeed, we saw the same ES promoter de-repression without readthrough when we depleted the cells for histone H3 (a core histone), suggesting that, though chromatin is clearly important to ES silencing, another layer of control exists.

This adds to the weight of evidence for the importance of chromatin in the maintenance VSG expression site silencing – fundamental to the effective monoallelic expression of this abundant family of T. brucei variant surface molecules. This work follows on from that of a number of other groups highlighting a multitude of expression site-influencing chromatin factors, including telomere binding proteins, histone deacetylases, other histone chaperones and components of the nuclear lamina (references below).

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