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Antigenic variation by malaria parasites: noncoding RNAs, histone modifiers and RNA pol II (232.2)
Author(s) -
Deitsch Kirk,
Ukaegbu Uchechi,
Kishore Sandeep
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.232.2
Subject(s) - biology , antigenic variation , gene , histone , genetics , gene expression , rna , regulation of gene expression
P. falciparum malaria parasites invade and ultimately destroy circulating red blood cells (RBCs) causing anemia and disrupted blood flow. As they develop, they place on the RBC surface the primary antigenic determinant, a protein referred to as PfEMP1. The var gene family is a large repertoire of genes encoding different variants of PfEMP1. Parasites only expresses a single var gene at a time while maintaining the remaining members of the family in a transcriptionally silent state. Switches in gene expression result in antigenic variation and allow the parasites to avoid the antibody response. var gene regulation is known to be dependent on specific histone modifications, however how various histone modifiers are specifically recruited to var loci remains a mystery. Our most recent work has focused on the histone modifier PfSET2. This protein is recruited to var loci and deposits the histone mark H3K36me3 at both silent and active var genes. PfSET2 binds directly to the C‐terminal domain of RNA pol II. RNA pol II is known to transcribe non‐coding RNAs from both active and silent var genes, providing a possible mechanism for recruitment of PfSET2 to var loci. Over‐expression of a dominant negative form of PfSET2 designed specifically to disrupt binding to RNA pol II induced rapid var gene expression switching, confirming both the importance of PfSET2 in var gene regulation and a role for RNA pol II in its recruitment.