title: Activation and clustering of a Plasmodium falciparum var gene are affected by subtelomeric sequences.
abstract: The Plasmodium falciparum var multigene family encodes the cytoadhesive, variant antigen PfEMP1. P. falciparum antigenic variation and cytoadhesion specificity are controlled by epigenetic switching between the single, or few, simultaneously expressed var genes. Most var genes are maintained in perinuclear clusters of heterochromatic telomeres. The active var gene(s) occupy a single, perinuclear var expression site. It is unresolved whether the var expression site forms in situ at a telomeric cluster or whether it is an extant compartment to which single chromosomes travel, thus controlling var switching. Here we show that transcription of a var gene did not require decreased colocalisation with clusters of telomeres, supporting var expression site formation in situ. However following recombination within adjacent subtelomeric sequences, the same var gene was persistently activated and did colocalise less with telomeric clusters. Thus, participation in stable, heterochromatic, telomere clusters and var switching are independent but are both affected by subtelomeric sequences. The var expression site colocalised with the euchromatic mark H3K27ac to a greater extent than it did with heterochromatic H3K9me3. H3K27ac was enriched within the active var gene promoter even when the var gene was transiently repressed in mature parasites and thus H3K27ac may contribute to var gene epigenetic memory.
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|The School of BioSciences, Bio21, The University of Melbourne, Victoria, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Duffy
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|The School of BioSciences, Bio21, The University of Melbourne, Victoria, Australia.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
authors.forename: Fransisca
authors.initials: F
authors.lastname: Sumardy
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|The School of BioSciences, Bio21, The University of Melbourne, Victoria, Australia.
authors.forename: Hanh H T
authors.initials: HH
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|The School of BioSciences, Bio21, The University of Melbourne, Victoria, Australia.
authors.forename: Shamista A
authors.initials: SA
authors.lastname: Selvarajah
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|Department of Biochemistry and Molecular Biology, The Pennsylvania State University, State College, PA, USA.
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: Josling
authors.affiliation: The School of BioSciences, Bio21, The University of Melbourne, Victoria, Australia.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Day
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Victoria, Australia.|The School of BioSciences, Bio21, The University of Melbourne, Victoria, Australia.
authors.forename: Michaela
authors.initials: M
authors.lastname: Petter
authors.affiliation: The Nossal Institute for Global Health, The University of Melbourne, Victoria, Australia.
authors.forename: Graham V
authors.initials: GV
authors.lastname: Brown
mesh_terms: D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000953:Antigens, Protozoan; D006570:Heterochromatin; D006657:Histones; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum
keywords: 
  FISH
  ; 
  Plasmodium falciparum
  ; chromatin; expression site; var genes