Genome-wide profiling of chromosome interactions in Plasmodium falciparum characterizes nuclear architecture and reconfigurations associated with antigenic variation.

Lemieux, J. E., Kyes, S. A., Otto, T. D. , Feller, A. I., Eastman, R. T., Pinches, R. A., Berriman, M., Su, X.-Z. and Newbold, C. I. (2013) Genome-wide profiling of chromosome interactions in Plasmodium falciparum characterizes nuclear architecture and reconfigurations associated with antigenic variation. Molecular Microbiology, 90(3), pp. 519-537. (PMID:23980881) (PMCID:PMC3894959)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Otto, Dr Thomas
Authors: Lemieux, J. E., Kyes, S. A., Otto, T. D., Feller, A. I., Eastman, R. T., Pinches, R. A., Berriman, M., Su, X.-Z., and Newbold, C. I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular Microbiology
Publisher:Blackwell Publishing
ISSN:0950-382X
ISSN (Online):1365-2958
Published Online:30 September 2013
Copyright Holders:Copyright ©2013 The Authors
First Published:First published in Molecular Microbiology 90(3): 519-537
Publisher Policy:Reproduced under a Creative Commons License

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