Abstract
The African sleeping sickness parasite Trypanosoma brucei evades the host immune system through antigenic variation of its variant surface glycoprotein (VSG) coat. Although the T. brucei genome contains ∼1500 VSGs, only one VSG is expressed at a time from one of about 15 subtelomeric VSG expression sites (ESs). For antigenic variation to work, not only must the vast VSG repertoire be kept silent in a genome that is mainly constitutively transcribed, but the frequency of VSG switching must be strictly controlled. Recently it has become clear that chromatin plays a key role in silencing inactive ESs, thereby ensuring monoallelic expression of VSG. We investigated the role of the linker histone H1 in chromatin organization and ES regulation in T. brucei. T. brucei histone H1 proteins have a different domain structure to H1 proteins in higher eukaryotes. However, we show that they play a key role in the maintenance of higher order chromatin structure in bloodstream form T. brucei as visualised by electron microscopy. In addition, depletion of histone H1 results in chromatin becoming generally more accessible to endonucleases in bloodstream but not in insect form T. brucei. The effect on chromatin following H1 knock-down in bloodstream form T. brucei is particularly evident at transcriptionally silent ES promoters, leading to 6–8 fold derepression of these promoters. T. brucei histone H1 therefore appears to be important for the maintenance of repressed chromatin in bloodstream form T. brucei. In particular H1 plays a role in downregulating silent ESs, arguing that H1-mediated chromatin functions in antigenic variation in T. brucei.
Highlights
The African trypanosome Trypanosoma brucei is a unicellular parasite causing African sleeping sickness, which is transmitted by tsetse flies in sub-Saharan Africa
Bloodstream form T. brucei is covered with a dense coat of variant surface glycoprotein (VSG)
The active VSG is transcribed in a telomeric VSG expression site (ES), and VSG switching allows immune evasion
Summary
The African trypanosome Trypanosoma brucei is a unicellular parasite causing African sleeping sickness, which is transmitted by tsetse flies in sub-Saharan Africa. For antigenic variation to work, it is key that only one VSG is expressed at a time, and the extensive repertoire of VSGs is kept transcriptionally silent These restrictions need to operate within the context of a T. brucei genome which is primarily organised as very extensive polycistronic transcription units constitutively expressed by Pol II [6,11]. It is unclear how ESs are controlled, it has recently been shown that chromatin remodeling must play a key role in their regulation [12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
