Monoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex
| Autor: | Faria, Joana, Glover, Lucy, Hutchinson, Sebastian, Boehm, Cordula, Field, Mark C., Horn, David |
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| Přispěvatelé: | University of Dundee, The work was funded by Wellcome Trust Investigator Awards to D.H. [100320/Z/12/Z] and M.C.F. [204697/Z/16/Z] with additional support from a Wellcome Trust Centre Award [203134/Z/16/Z]. The University of Dundee Flow Cytometry and Imaging Facilities are supported by a Wellcome Trust award [097418/Z/11/Z], and the MRC Next Generation Optical Microscopy award [MR/K015869/1], respectively, while both the Proteomics and Imaging Facilities are supported by a Wellcome Trust Technology Platform award [097945/B/11/Z]. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
DNA Replication
Transcription Genetic Science [SDV]Life Sciences [q-bio] Trypanosoma brucei brucei Protozoan Proteins MESH: DNA Replication MESH: Host-Parasite Interactions Article Cell Line Epigenesis Genetic Host-Parasite Interactions parasitic diseases Parasite genetics Animals MESH: Animals MESH: Epigenesis Genetic MESH: Immune Evasion lcsh:Science MESH: Protozoan Proteins Alleles Immune Evasion MESH: Alleles MESH: Transcription Genetic MESH: Trypanosoma brucei brucei Gene silencing MESH: Gene Expression Regulation Antigenic Variation MESH: Cell Line Parasite biology Chromatin Assembly Factor-1 MESH: Trypanosomiasis African Trypanosomiasis African Gene Expression Regulation MESH: Antigenic Variation MESH: Variant Surface Glycoproteins Trypanosoma lcsh:Q Epigenetics analysis MESH: Chromatin Assembly Factor-1 Variant Surface Glycoproteins Trypanosoma |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.3023. ⟨10.1038/s41467-019-10823-8⟩ |
| ISSN: | 2041-1723 |
| Popis: | The largest gene families in eukaryotes are subject to allelic exclusion, but mechanisms underpinning single allele selection and inheritance remain unclear. Here, we describe a protein complex sustaining variant surface glycoprotein (VSG) allelic exclusion and antigenic variation in Trypanosoma brucei parasites. The VSG-exclusion-1 (VEX1) protein binds both telomeric VSG-associated chromatin and VEX2, an ortholog of nonsense-mediated-decay helicase, UPF1. VEX1 and VEX2 assemble in an RNA polymerase-I transcription-dependent manner and sustain the active, subtelomeric VSG-associated transcription compartment. VSG transcripts and VSG coats become highly heterogeneous when VEX proteins are depleted. Further, the DNA replication-associated chromatin assembly factor, CAF-1, binds to and specifically maintains VEX1 compartmentalisation following DNA replication. Thus, the VEX-complex controls VSG-exclusion, while CAF-1 sustains VEX-complex inheritance in association with the active-VSG. Notably, the VEX2-orthologue and CAF-1 in mammals are also implicated in exclusion and inheritance functions. In trypanosomes, these factors sustain a highly effective and paradigmatic immune evasion strategy. Monoallelic expression of variant surface glycoprotein genes (VSGs) is essential for immune evasion by Trypanosoma brucei. Here, Faria et al. show that the VEX protein complex controls VSG allelic exclusion, and that CAF‐1 sustains inheritance of the VEX‐complex in association with the active VSG. |
| Databáze: | OpenAIRE |
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