PfSET10, a Plasmodium falciparum Methyltransferase, Maintains the Active var Gene in a Poised State during Parasite Division

Jennifer C. Volz; Richard Bártfai; Michaela Petter; Christine Langer; Gabrielle A. Josling; Takafumi Tsuboi; Frank Schwach; Jake Baum; Julian C. Rayner; Henk G. Stunnenberg; Michael F. Duffy; Alan F. Cowman

doi:10.1016/j.chom.2011.11.011

PfSET10, a Plasmodium falciparum Methyltransferase, Maintains the Active var Gene in a Poised State during Parasite Division

Jennifer C. Volz, Richard Bártfai, Michaela Petter, Christine Langer, Gabrielle A. Josling, Takafumi Tsuboi, Frank Schwach, Jake Baum, Julian C. Rayner, Henk G. Stunnenberg, Michael F. Duffy, Alan F. Cowman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

112 Citations (Scopus)

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.

Original language	English
Pages (from-to)	7-18
Number of pages	12
Journal	Cell Host and Microbe
Volume	11
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2011.11.011
Publication status	Published - 19 Jan 2012
Externally published	Yes

Bibliographical note

Funding 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.

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10.1016/j.chom.2011.11.011

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Volz, J. C., Bártfai, R., Petter, M., Langer, C., Josling, G. A., Tsuboi, T., Schwach, F., Baum, J., Rayner, J. C., Stunnenberg, H. G., Duffy, M. F., & Cowman, A. F. (2012). PfSET10, a Plasmodium falciparum Methyltransferase, Maintains the Active var Gene in a Poised State during Parasite Division. Cell Host and Microbe, 11(1), 7-18. https://doi.org/10.1016/j.chom.2011.11.011

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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.",

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PfSET10, a Plasmodium falciparum Methyltransferase, Maintains the Active var Gene in a Poised State during Parasite Division

Abstract

Bibliographical note

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