title: Plasmodium falciparum centromeres display a unique epigenetic makeup and cluster prior to and during schizogony.
abstract: Centromeres are essential for the faithful transmission of chromosomes to the next generation, therefore being essential in all eukaryotic organisms. The centromeres of Plasmodium falciparum, the causative agent of the most severe form of malaria, have been broadly mapped on most chromosomes, but their epigenetic composition remained undefined. Here, we reveal that the centromeric histone variant PfCENH3 occupies a 4-4.5 kb region on each P. falciparum chromosome, which is devoid of pericentric heterochromatin but harbours another histone variant, PfH2A.Z. These CENH3 covered regions pinpoint the exact position of the centromere on all chromosomes and revealed that all centromeric regions have similar size and sequence composition. Immunofluorescence assay of PfCENH3 strongly suggests that P. falciparum centromeres cluster to a single nuclear location prior to and during mitosis and cytokinesis but dissociate soon after invasion. In summary, we reveal a dynamic association of Plasmodium centromeres, which bear a unique epigenetic signature and conform to a strict structure. These findings suggest that DNA-associated and epigenetic elements play an important role in centromere establishment in this important human pathogen.
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Wieteke A M
authors.initials: WA
authors.lastname: Hoeijmakers
authors.forename: Christian
authors.initials: C
authors.lastname: Flueck
authors.forename: Kees-Jan
authors.initials: KJ
authors.lastname: Françoijs
authors.forename: Arne H
authors.initials: AH
authors.lastname: Smits
authors.forename: Johanna
authors.initials: J
authors.lastname: Wetzel
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Volz
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.forename: Till
authors.initials: T
authors.lastname: Voss
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Richárd
authors.initials: R
authors.lastname: Bártfai
mesh_terms: D002503:Centromere / Q000378:metabolism*; D048749:Cytokinesis; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D016054:DNA, Protozoan; D006657:Histones; D015800:Protozoan Proteins