A histone methyltransferase modulates antigenic variation in African trypanosomes

• Published in: PLoS biology Vol. 6; no. 7; p. e161
• Main Authors: Figueiredo, Luisa M, Janzen, Christian J, Cross, George A M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-07-2008; Public Library of Science (PLoS)
• Subjects: Animals; Antigenic Variation - genetics; Antigenic Variation - immunology; Cell Biology; Cell cycle; Cloning; DNA methylation; Epigenetics; Gene expression; Gene Expression Regulation, Enzymologic - immunology; Gene Silencing; Genetics; Genetics and Genomics; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Host-Parasite Interactions; Infectious Diseases; Microbiology; Microscopy; Molecular Biology; Parasites; Protein Methyltransferases; RNA polymerase; Trypanosoma brucei; Trypanosoma brucei brucei - enzymology; Trypanosoma brucei brucei - pathogenicity; Trypanosoma brucei brucei - physiology; Variant Surface Glycoproteins, Trypanosoma - genetics; Variant Surface Glycoproteins, Trypanosoma - immunology; Yeast; Gene Expression Regulation, Enzymologic; Protein Methyltransferases; Animals; Antigenic Variation; Histone-Lysine N-Methyltransferase; Gene Silencing; Variant Surface Glycoproteins, Trypanosoma; Host-Parasite Interactions; Trypanosoma brucei brucei
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.0060161

To evade the host immune system, several pathogens periodically change their cell-surface epitopes. In the African trypanosomes, antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins (VSGs). Immune evasion relies on two important features: exposing a single type of VSG at the cell surface and periodically and very rapidly switching the expressed VSG. Transcriptional switching between resident telomeric VSG genes does not involve DNA rearrangements, and regulation is probably epigenetic. The histone methyltransferase DOT1B is a nonessential protein that trimethylates lysine 76 of histone H3 in Trypanosoma brucei. Here we report that transcriptionally silent telomeric VSGs become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected. DOT1B also is involved in the kinetics of VSG switching: in DeltaDOT1B cells, the transcriptional switch is so slow that cells expressing two VSGs persist for several weeks, indicating that monoallelic transcription is compromised. We conclude that DOT1B is required to maintain strict VSG silencing and to ensure rapid transcriptional VSG switching, demonstrating that epigenetics plays an important role in regulating antigenic variation in T. brucei.