Effect of I-BET151 on insect stage Trypanosoma brucei

The eukaryotic protozoan parasite Trypanosoma brucei is transmitted by the tsetse fly to the bloodstream of both humans and animals, causing African trypanosomiasis. Chemical inhibition of chromatin interacting bromodomain proteins has previously been shown to perturb bloodstream specific trypanosome processes, including silencing of the Variant Surface Glycoprotein genes (VSGs) and immune evasion. We performed RNA-seq timecourses to determine the effects of chemical bromodomain inhibition in insect stage parasites using the compound I-BET151. We found that treatment with I-BET151 causes large changes in the transcriptome of insect stage parasites, and also perturbs silencing of VSG genes. The transcriptomes of bromodomain inhibited parasites share some features with early metacyclic stage parasites in the fly salivary gland, implicating bromodomain proteins as important for regulating transcript levels for developmentally relevant genes. Understanding the gene regulatory processes that facilitate transcriptome remodeling in this highly diverged eukaryote may shed light on how these mechanisms evolved.