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Published online on January 5, 2007, 10.1073/pnas.0609084103 OPEN ACCESS ARTICLE


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Genetics
Epigenetic memory at malaria virulence genes

( antigenic variation | chromatin | monoallelic expression | histone modification )

Thanat Chookajorn *{dagger}{ddagger}, Ron Dzikowski {sect}, Matthias Frank {sect}¶||, Felomena Li {sect}, Alisha Z. Jiwani *, Daniel L. Hartl *{ddagger}, and Kirk W. Deitsch {sect}

*Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138; {dagger}Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10700, Thailand; {sect}Department of Microbiology and Immunology and Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, NY 10021; and ||Institute for Tropical Medicine, University of Tuebingen, 72016 Tuebingen, Germany

Contributed by Daniel L. Hartl, October 16, 2006 (sent for review September 14, 2006)

During its red blood cell stage, the malaria parasite Plasmodium falciparum can switch its variant surface proteins (P. falciparum erythrocyte membrane protein 1) to evade the host immune response. The var gene family encodes P. falciparum erythrocyte membrane protein 1, different versions of which have unique binding specificities to various human endothelial surface molecules. Individual parasites each contain {approx}60 var genes at various locations within their chromosomes; however, parasite isolates contain different complements of var genes, thus, the gene family is enormous with a virtually unlimited number of members. A single var gene is expressed by each parasite in a mutually exclusive manner. We report that control of var gene transcription and antigenic variation is associated with a chromatin memory that includes methylation of histone H3 at lysine K9 as an epigenetic mark. We also discuss how gene transcription memory may affect the mechanism of pathogenesis and immune evasion.

Author contributions: T.C., D.L.H., and K.W.D. designed research; T.C., R.D., M.F., F.L., and A.Z.J. performed research; R.D. and M.F. contributed new reagents/analytic tools; T.C., R.D., M.F., F.L., A.Z.J., D.L.H., and K.W.D. analyzed data; and T.C., D.L.H., and K.W.D. wrote the paper.

The authors declare no conflict of interest.

Freely available online through the PNAS open access option.

{ddagger}To whom correspondence may be addressed.

Thanat Chookajorn, E-mail: chookaj{at}fas.harvard.edu
Daniel L. Hartl, E-mail: dhartl{at}oeb.harvard.edu

www.pnas.org/cgi/doi/10.1073/pnas.0609084103
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