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.
Bibliographical noteFunding Information:
We thank Stefan Glaser (WEHI, Melbourne) for helpful discussions and the Red Cross Blood Service (Australia) for blood. This work was supported by the National Health and Medical Research Council of Australia (NHMRC). A.F.C. is an Australia Fellow of the NHMRC. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. J.C.V. was supported by a HFSP long-term fellowship. Work in the Stunnenberg laboratory was supported by EVIMalaR.