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| Subject Categories: Microbiology & Pathogens |
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| The EMBO Journal
(2007) 26, 2400–2410, doi:10.1038/sj.emboj.7601678 Published online 12 April 2007 |
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| A novel ISWI is involved in VSG expression site downregulation in African trypanosomes |
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| Katie Hughes1, Matthew Wand1, Lucy Foulston1, Rosanna Young1, Kate Harley1, Stephen Terry1, Klaus Ersfeld2 and Gloria Rudenko1 |
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1 Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK 2 Department of Biological Sciences, University of Hull, Hull, UK To whom correspondence should be addressed Gloria Rudenko, The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, UK. Tel.: +44 1865 281 548; Fax: +44 1865 281 894; E-mail: gloria.rudenko@medawar.ox.ac.uk Received 8 January 2007; Accepted 15 March 2007; Published online 12 April 2007. |
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| Abstract |
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| African trypanosomes show monoallelic expression of one of about 20 telomeric variant surface glycoprotein (VSG) gene-expression sites (ESs) while multiplying in the mammalian bloodstream. We screened for genes involved in ES silencing using flow cytometry and RNA interference (RNAi). We show that a novel member of the ISWI family of SWI2/SNF2-related chromatin-remodelling proteins (TbISWI) is involved in ES downregulation in Trypanosoma brucei. TbISWI has an atypical protein architecture for an ISWI, as it lacks characteristic SANT domains. Depletion of TbISWI by RNAi leads to 30–60-fold derepression of ESs in bloodstream-form T. brucei, and 10–17-fold derepression in insect form T. brucei. We show that although blocking synthesis of TbISWI leads to derepression of silent VSG ES promoters, this does not lead to fully processive transcription of silent ESs, or an increase in ES-activation rates. VSG ES activation in African trypanosomes therefore appears to be a multistep process, whereby an increase in transcription from a silent ES promoter is necessary but not sufficient for full ES activation. |
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| Keywords: antigenic variation, ISWI, monoallelic expression, regulated domains, Trypanosoma brucei |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHA novel ISWI is involved in VSG expression site downregulation in African trypanosomes The EMBO Journal Article Position-dependent and promoter-specific regulation of gene expression in Trypanosoma brucei The EMBO Journal Article (15 Dec 1997) The EMBO Journal Article (15 Apr 1999) Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex The EMBO Journal Article (28 Nov 2007) |
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