Epigenetic memory at malaria virulence genes.
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 approximately 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.
Chookajorn
Thanat
T
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. chookaj@fas.harvard.edu
Dzikowski
Ron
R
Frank
Matthias
M
Li
Felomena
F
Jiwani
Alisha Z
AZ
Hartl
Daniel L
DL
Deitsch
Kirk W
KW
D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D008288:Malaria / Q000276:immunology / Q000469:parasitology*; D008745:Methylation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D014158:Transcription, Genetic / Q000235:genetics; D014774:Virulence / Q000235:genetics
D002843:Chromatin; D006657:Histones