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dc.contributor.authorRosenberg, E
dc.contributor.authorBen-Shmuel, A
dc.contributor.authorShalev, O
dc.contributor.authorSinay, R
dc.contributor.authorCowman, A
dc.contributor.authorPollack, Y
dc.date.accessioned2020-12-21T03:24:14Z
dc.date.available2020-12-21T03:24:14Z
dc.date.issued2009-09-10
dc.identifier.citationRosenberg, E., Ben-Shmuel, A., Shalev, O., Sinay, R., Cowman, A. & Pollack, Y. (2009). Differential, Positional-Dependent Transcriptional Response of Antigenic Variation (var) Genes to Biological Stress in Plasmodium falciparum. PLOS ONE, 4 (9), https://doi.org/10.1371/journal.pone.0006991.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/257190
dc.description.abstract1% of the genes of the human malaria causing agent Plasmodium falciparum belong to the heterogeneous var gene family which encodes P. falciparum erythrocyte membrane protein 1 (PFEMP1). This protein mediates part of the pathogenesis of the disease by causing adherence of infected erythrocytes (IE) to the host endothelium. At any given time, only one copy of the family is expressed on the IE surface. The cues which regulate the allelic exclusion of these genes are not known. We show the existence of a differential expression pattern of these genes upon exposure to biological stress in relation to their positional placement on the chromosome - expression of centrally located var genes is induced while sub-telomeric copies of the family are repressed - this phenomenon orchestrated by the histone deacetylase pfsir2. Moreover, stress was found to cause a switch in the pattern of the expressed var genes thus acting as a regulatory cue. By using pharmacological compounds which putatively affect pfsir2 activity, distinct changes of var gene expression patterns were achieved which may have therapeutic ramifications. As disease severity is partly associated with expression of particular var gene subtypes, manipulation of the IE environment may serve as a mechanism to direct transcription towards less virulent genes.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.titleDifferential, Positional-Dependent Transcriptional Response of Antigenic Variation (var) Genes to Biological Stress in Plasmodium falciparum
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0006991
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titlePLoS One
melbourne.source.volume4
melbourne.source.issue9
dc.rights.licenseCC BY
melbourne.elementsid1252109
melbourne.contributor.authorCowman, Alan
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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