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Clonally variant gene families in Plasmodium falciparum share a common activation factor.

TitleClonally variant gene families in Plasmodium falciparum share a common activation factor.
Publication TypeJournal Article
Year of Publication2009
AuthorsHowitt CA, Wilinski D, LlinĂ¡s M, Templeton TJ, Dzikowski R, Deitsch KW
JournalMol Microbiol
Volume73
Issue6
Pagination1171-85
Date Published2009 Sep
ISSN1365-2958
KeywordsAnimals, Gene Expression Regulation, Genes, Protozoan, Models, Biological, Plasmodium falciparum, Promoter Regions, Genetic, Protozoan Proteins, Transcriptional Activation
Abstract

The genome of the malaria parasite Plasmodium falciparum contains several multicopy gene families, including var, rifin, stevor and Pfmc-2TM. These gene families undergo expression switching and appear to play a role in antigenic variation. It has recently been shown that forcing parasites to express high copy numbers of transcriptionally active, episomal var promoters led to gradual downregulation and eventual silencing of the entire var gene family, suggesting that a limiting titratable factor plays a role in var gene activation. Through similar experiments using rifin, stevor or Pfmc-2TM episomal promoters we show that promoter titration can be used as a general method to downregulate multicopy gene families in P. falciparum. Additionally, we show that promoter titration with var, rifin, stevor or Pfmc-2TM episomal promoters results in downregulation of expression not only of the family to which the episomal promoter belongs, but also members of the other gene families, suggesting that the var-specific titratable factor previously described is shared by all four families. Further, transcriptionally active promoters from different families colocalize within the same subnuclear expression site, indicating that the role that nuclear architecture plays in var gene regulation also likely applies to the other multicopy gene families of P. falciparum.

DOI10.1111/j.1365-2958.2009.06846.x
Alternate JournalMol Microbiol
PubMed ID19708920
PubMed Central IDPMC2752644
Grant ListR01 AI052390 / AI / NIAID NIH HHS / United States
R01 AI052390-08 / AI / NIAID NIH HHS / United States

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