The function of histone H3 lysine 76 methylation in host-induced differentiation in Trypanosoma brucei

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Trypanosomes are mammalian pathogens with a complex parasitic life cycle in different hosts. Changes in gene expression profiles that result in specialized life cycle stages are crucial to adapt to very different host environments. Trypanosomes mainly regulate mRNA levels by posttranscriptional mechanisms. Nevertheless, there is increasing evidence that changes in chromatin structure are correlated with differential gene activity during stage differentiation. Furthermore, trypanosome histones carry multiple post-translational modifications, some of which are involved in transcriptional regulation in other organisms. The first direct evidence that histone modifications are involved in the differentiation process was provided by targeted deletion of the histone methyltransferase DOT1B which resulted in the inability of bloodstream stage parasites to differentiate to fly midgut stages. In this project, we will investigate changes in the nuclear architecture during host-induced differentiation, specifically the subnuclear distribution of histone modifications, and the assignment of specific modifications to the activity status of differentially regulated genes. We will test the hypothesis that chromatin remodeling is involved in the regulation of gene expression triggered by the host environment.