Chromatin structure in African trypanosomes
Trypanosomes have developed a remarkable strategy for escaping host immune responses by periodically changing the variant surface glycoprotein (VSG) expressed on the surface of the parasite. Although there are hundreds of VSG genes in the genome, the bloodstream form of the parasite expresses only one gene at a time. Gene expression is tightly linked with chromatin structure and the accessibility of the transcribed regions by various transcription factors. Chromatin remodelling is driven by specialised proteins that modify associated histones. Accumulating evidence indicates that histone H1 can negatively or positively regulate gene transcription. The scope of the EU-funded 'Chromatin and antigenic variation: The role of histone H1 in gene regulation in African trypanosomes' (HISTONEH1TRYP) project was to elucidate the mechanism behind this VSG monoallelic expression. The work focused on histone H1 and how it controls antigenic variation in T.brucei. Experimental data indicated that although histone H1 is dispensable for parasite growth in culture, it determines parasite fitness in vivo. Histone H1 works by compacting chromatin at various regions throughout the parasite genome and thereby regulates transcription of various genes including VSG. Collectively, the findings of the HISTONEH1TRYP project unveil a novel function of histone H1 in the antigenic variation and immune evasion of T.brucei. This information could form the basis for the design of novel therapeutics targeting histone H1 modifications.
Keywords
African sleeping sickness, Trypanosoma brucei, VSG, chromatin, antigenic variation