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      Nuclear phosphatidylinositol 5-phosphatase is essential for allelic exclusion of variant surface glycoprotein genes in trypanosomes

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      Molecular and Cellular Biology
      American Society for Microbiology

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          Abstract

          Allelic exclusion of variant surface glycoprotein (VSG) genes is essential for African trypanosomes to evade the host antibody response by antigenic variation. The mechanisms by which this parasite expresses only one of its ∼2,000 VSG genes at a time are unknown. We show that nuclear phosphatidylinositol 5-phosphatase (PIP5Pase) interacts with repressor activator protein 1 (RAP1) in a multiprotein complex and function in the control of VSG allelic exclusion. RAP1 binds PIP5Pase substrate, PI(3,4,5)P3, and catalytic mutation of PIP5Pase that inhibits PI(3,4,5)P3 dephosphorylation results in simultaneous transcription of VSGs from all telomeric expression sites (ES) and from silent subtelomeric VSG arrays. PIP5Pase and RAP1 bind to telomeric ESs, especially at 70bp repeats and telomeres, and their binding is altered by PIP5Pase inactivation or knockdown implying changes in ES chromatin organization. Our data suggest a model whereby PIP5Pase controls PI(3,4,5)P3 binding by RAP1, and thus RAP1 silencing of telomeric and subtelomeric VSG genes. Allelic exclusion of VSG genes may hence entail control of nuclear phosphoinositides.

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          Author and article information

          Journal
          Molecular and Cellular Biology
          Mol Cell Biol
          American Society for Microbiology
          0270-7306
          1098-5549
          November 12 2018
          Article
          10.1128/MCB.00395-18
          6336139
          30420356
          1454f7b7-831a-4dc7-a63b-eb626170273c
          © 2018
          History

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