Affiliation:
1. Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, W-704, Box 62, New York, New York 10021
Abstract
ABSTRACT
Antigenic variation in the human malaria parasite
Plasmodium falciparum
depends on the transcriptional regulation of the
var
gene family. In each individual parasite, mRNA is expressed exclusively from 1
var
gene out of ∼60, while the rest of the genes are transcriptionally silenced. Both modifications to chromatin structure and DNA regulatory elements associated with each
var
gene have been implicated in the organization and maintenance of the silent state. Whether silencing is established at the level of entire chromosomal regions via heterochromatin spreading or at the level of individual
var
promoters through the action of a silencing element within each
var
intron has been debated. Here, we consider both possibilities, using clonal parasite lines carrying chromosomally integrated transgenes. We confirm a previous finding that the loss of an adjacent
var
intron results in
var
promoter activation and further show that transcriptional activation of a
var
promoter within a cluster does not affect the transcriptional activity of neighboring
var
promoters. Our results provide more evidence for the hypothesis that
var
genes are primarily silenced at the level of an individual gene, rather than by heterochromatin spreading. We also tested the intrinsic directionality of an intron's silencing effect on upstream or downstream
var
promoters. We found that an intron is capable of silencing in either direction and that, once established, a
var
promoter-intron pair is stably maintained through many generations, suggesting a possible role in epigenetic memory. This study provides insights into the regulation of endogenous
var
gene clusters.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Cited by
24 articles.
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