title: PfSET10, a Plasmodium falciparum methyltransferase, maintains the active var gene in a poised state during parasite division.
abstract: A major virulence factor of the malaria parasite Plasmodium falciparum is erythrocyte membrane protein 1 (PfEMP1), a variant protein expressed on the infected erythrocyte surface. PfEMP1 is responsible for adherence of infected erythrocytes to the endothelium and plays an important role in pathogenesis. Mutually exclusive transcription and switched expression of one of 60 var genes encoding PfEMP1 in each parasite genome provides a mechanism for antigenic variation. We report the identification of a parasite protein, designated PfSET10, which localizes exclusively to the perinuclear active var gene expression site. PfSET10 is a histone 3 lysine 4 methyltransferase required to maintain the active var gene in a poised state during division for reactivation in daughter parasites, and as such is required for P. falciparum antigenic variation. PfSET10 likely maintains the transcriptionally permissive chromatin environment of the active var promoter and thus retains memory for heritable transmission of epigenetic information during parasite division.
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Volz
authors.forename: Richard
authors.initials: R
authors.lastname: Bártfai
authors.forename: Michaela
authors.initials: M
authors.lastname: Petter
authors.forename: Christine
authors.initials: C
authors.lastname: Langer
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: Josling
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Frank
authors.initials: F
authors.lastname: Schwach
authors.forename: Jake
authors.initials: J
authors.lastname: Baum
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: Henk G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Michael F
authors.initials: MF
authors.lastname: Duffy
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000940:Antigenic Variation; D002455:Cell Division; D016054:DNA, Protozoan / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D011495:Histone-Lysine N-Methyltransferase