Key Points
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Trypanosoma brucei, the causative agent of sleeping sickness in humans, diverged from the highest eukaryotic lineage several hundred million years ago. Understanding epigenetic regulation in T. brucei could shed light on important basic questions in the chromatin field.
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Edman degradation and mass spectrometry studies revealed a striking absence of many well-conserved histone post-translational modifications (PTMs). By contrast, some unusual and apparently trypanosome-specific PTMs were identified. DNA can also carry epigenetic information, either in the form of methylcytosine or base J.
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Consistent with a simplified histone code, the genome of T. brucei contains few candidate genes that encode for histone-modifying or chromatin-remodelling enzymes. Readers of the histone code can also be identified, and they seem to have a single PTM-binding domain.
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Characterization of some of these epigenetic factors revealed that they are involved in the regulation of VSG monoallelic expression and cell differentiation cell cycle control.
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Future studies should lead to the identification of more players involved in epigenetics in T. brucei, as well as the mechanistic details of how they regulate basic biological processes.
Abstract
Epigenetic regulation is important in many facets of eukaryotic biology. Recent work has suggested that the basic mechanisms underlying epigenetic regulation extend to eukaryotic parasites. The identification of post-translational histone modifications and chromatin-modifying enzymes is beginning to reveal both common and novel functions for chromatin in these parasites. In this Review, we compare the role of epigenetics in African trypanosomes and humans in several biological processes. We discuss how the study of trypanosome chromatin might help us to better understand the evolution of epigenetic processes.
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Acknowledgements
The authors thank S. Hake and N. Siegel for their critical reading of the manuscript; G. Rudenko and R. Sabatini for helpful comments; and P. Bastin and B. Rotureau for providing micrographs of the different stages of the T. brucei life cycle, which were used, in part, to draw the cartoons in Table 1.
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Glossary
- Post-translational modification
-
An enzymatic modification of an amino acid residue that occurs after a protein is synthesized, and often modifies the function or lifespan of a protein.
- Variant surface glycoprotein
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(VSG). The most abundant protein (approximately 10 million identical copies on individual cells) at the surface of the bloodstream slender, stumpy and metacyclic life cycle stages of Trypanosoma brucei. Periodic change of the VSG surface coat is a crucial part of the evasion mechanism known as antigenic variation.
- Tsetse
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The insect vector (Glossina spp.) that ensures the transmission of Trypanosoma brucei between two mammalian hosts. The word tsetse means fly and it originates from the Tswana language.
- Procyclin
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The most abundant protein at the surface of the procyclic life cycle form. There are two types of procyclin: EP and GPEET. These glycosylated proteins are not subject to allelic exclusion.
- Epimastigote
-
The Trypanosoma brucei life cycle stage that colonizes the tsetse salivary glands.
- Metacyclic
-
The Trypanosoma brucei life cycle stage in the tsetse salivary glands that reinfects the mammalian host.
- Edman degradation
-
A method developed by P. Edman to sequence peptides by sequential labelling and cleavage of single residues from the amino-terminal end of polypeptides.
- Euchromatin
-
A form of chromatin that was first defined as lightly stained nuclear regions by light microscopy and is usually associated with transcriptionally competent chromosome loci.
- Heterochromatin
-
A more compact form of chromatin that, when using light or electron microscopy, appears as darker regions of the nucleus. Heterochromatinis usually associated with transcriptionally silent chromosome loci.
- Antigenic variation
-
The process by which an infectious organism alters its surface to evade the host immune response; common in several pathogens, such as Trypanosoma brucei, the malaria parasite Plasmodium falciparum and Giardia lamblia.
- Monoallelic expression
-
The expression of a single allele from a gene family.
- Triton acid urea gel electrophoresis
-
A polyacrylamide gel-based electrophoresis technique that allows the efficient separation of core histones as a result of their association with Triton X- 100.
- Karyokinesis
-
The process that partitions of the nucleus into the daughter cells during cell division.
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Figueiredo, L., Cross, G. & Janzen, C. Epigenetic regulation in African trypanosomes: a new kid on the block. Nat Rev Microbiol 7, 504–513 (2009). https://doi.org/10.1038/nrmicro2149
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DOI: https://doi.org/10.1038/nrmicro2149
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