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Trypanosoma brucei is a unicellular parasite that causes sleeping sickness in humans. Most of its transcription is constitutive and driven by RNA polymerase II. RNA polymerase I (Pol I) transcribes not only ribosomal RNA genes, but also protein-encoding genes, including variant surface glycoproteins (VSGs) and procyclins. In T. brucei, histone H1 (H1) is required for VSG silencing and chromatin condensation. However, whether H1 has a genome-wide role in transcription is unknown. Here, using RNA sequencing we show that H1 depletion changes the expression of a specific cohort of genes. Interestingly, the predominant effect is partial loss of silencing of Pol I loci, such as VSG and procyclin genes. Labelling of nascent transcripts with 4-thiouridine showed that H1 depletion does not alter the level of labelled Pol II transcripts. In contrast, the levels of 4sU-labelled Pol I transcripts were increased by two- to sixfold, suggesting that H1 preferentially blocks transcription at Pol I loci. Finally, we observed that parasites depleted of H1 grow almost normally in culture but they have a reduced fitness in mice, suggesting that H1 is important for host-pathogen interactions.

T rypanosoma brucei is a unicellular parasite that causes sleeping sickness in humans. Most of its transcription is constitutive and driven by RNA polymerase II. RNA polymerase I ( Pol I) transcribes not only ribosomal RNA genes, but also protein-encoding genes, including variant surface glycoproteins ( VSGs) and procyclins. In T . brucei, histone H1 ( H1) is required for VSG silencing and chromatin condensation. However, whether H1 has a genome-wide role in transcription is unknown. Here, using RNA sequencing we show that H1 depletion changes the expression of a specific cohort of genes. Interestingly, the predominant effect is partial loss of silencing of Pol I loci, such as VSG and procyclin genes. Labelling of nascent transcripts with 4-thiouridine showed that H1 depletion does not alter the level of labelled Pol II transcripts. In contrast, the levels of 4 sU-labelled Pol I transcripts were increased by two- to sixfold, suggesting that H1 preferentially blocks transcription at Pol I loci. Finally, we observed that parasites depleted of H1 grow almost normally in culture but they have a reduced fitness in mice, suggesting that H1 is important for host-pathogen interactions. [ABSTRACT FROM AUTHOR]

Trypanosomal infection-induced anaemia is a devastating scourge for cattle in widespread regions. Although Trypanosoma vivax is considered as one of the most important parasites regarding economic impact in Africa and South America, very few in-depth studies have been conducted due to the difficulty of manipulating this parasite. Several hypotheses were proposed to explain trypanosome induced-anaemia but mechanisms have not yet been elucidated. Here, we characterized a multigenic family of trans-sialidases in T. vivax, some of which are released into the host serum during infection. These enzymes are able to trigger erythrophagocytosis by desialylating the major surface erythrocytes sialoglycoproteins, the glycophorins. Using an ex vivo assay to quantify erythrophagocytosis throughout infection, we showed that erythrocyte desialylation alone results in significant levels of anaemia during the acute phase of the disease. Characterization of virulence factors such as the trans-sialidases is vital to develop a control strategy against the disease or parasite. [ABSTRACT FROM AUTHOR]