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Spatial relationships within the eukaryotic nucleus are essential for proper nuclear function. In Plasmodium falciparum, the repositioning of chromosomes has been implicated in the regulation of the expression of genes responsible for antigenic variation, and the formation of a single, peri-nuclear nucleolus results in the clustering of rDNA. Nevertheless, the precise spatial relationships between chromosomes remain poorly understood, because, until recently, techniques with sufficient resolution have been lacking. Here we have used chromosome conformation capture and second-generation sequencing to study changes in chromosome folding and spatial positioning that occur during switches in var gene expression. We have generated maps of chromosomal spatial affinities within the P. falciparum nucleus at 25 Kb resolution, revealing a structured nucleolus, an absence of chromosome territories, and confirming previously identified clustering of heterochromatin foci. We show that switches in var gene expression do not appear to involve interaction with a distant enhancer, but do result in local changes at the active locus. These maps reveal the folding properties of malaria chromosomes, validate known physical associations, and characterize the global landscape of spatial interactions. Collectively, our data provide critical information for a better understanding of gene expression regulation and antigenic variation in malaria parasites.

Original publication

DOI

10.1111/mmi.12381

Type

Journal article

Journal

Mol Microbiol

Publication Date

11/2013

Volume

90

Pages

519 - 537

Keywords

Antigenic Variation, Cell Nucleolus, Chromosome Mapping, Chromosomes, DNA, Protozoan, DNA, Ribosomal, Enhancer Elements, Genetic, Gene Expression Regulation, Genetic Loci, Genome, Protozoan, Models, Genetic, Nucleic Acid Conformation, Plasmodium falciparum, Protozoan Proteins, Sequence Analysis, DNA