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Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron.

TitlePlasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron.
Publication TypeJournal Article
Year of Publication2003
AuthorsCalderwood MS, Gannoun-Zaki L, Wellems TE, Deitsch KW
JournalJ Biol Chem
Volume278
Issue36
Pagination34125-32
Date Published2003 Sep 05
ISSN0021-9258
KeywordsAlleles, Animals, Antigens, Base Sequence, Cell Cycle, Chromatin, Exons, Gene Expression Regulation, Gene Silencing, Introns, Luciferases, Molecular Sequence Data, Plasmids, Plasmodium falciparum, Promoter Regions, Genetic, RNA, Messenger, S Phase, Sequence Homology, Nucleic Acid, Telomere, Transcription, Genetic, Transfection
Abstract

Antigenic variation in Plasmodium falciparum malaria parasites results from switches in expression among members of the multicopy var gene family. This family is subject to allelic exclusion by which particular genes are expressed while the rest of the family remains transcriptionally silent. Evidence from reporter constructs indicates that var gene silencing involves a cooperative interaction between the var intron and an upstream element and requires transition of the parasites through S-phase of the cell cycle. These findings implicate chromatin assembly in the process of regulating var gene expression and antigenic variation. Here we characterize the var intron and the elements within it that are necessary for var transcriptional silencing. Alignments of var introns show a highly conserved structure that consists of three discreet regions with distinct base pair compositions. The middle region is highly AT-rich and is sufficient to silence an associated var promoter. Constructs that include a typical var intron upstream of a reporter gene or drug-selectable marker reveal that the intron also possesses promoter activity, presumably providing an explanation for the origin of the previously described var "sterile" transcripts. Deletions that disable the promoter activity of the intron also eliminate its ability to function as a silencer. These findings suggest that interactions between the regions of these two promoters and the generation of the sterile transcripts play a significant role in regulating var gene expression.

DOI10.1074/jbc.M213065200
Alternate JournalJ Biol Chem
PubMed ID12832422
Grant ListAI 52390 / AI / NIAID NIH HHS / United States

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