title: Alterations in local chromatin environment are involved in silencing and activation of subtelomeric var genes in Plasmodium falciparum.
abstract: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var gene family, undergoes antigenic variation and plays an important role in chronic infection and severe malaria. Only a single var gene is transcribed per parasite, and epigenetic control mechanisms are fundamental in this strategy of mutually exclusive transcription. We show that subtelomeric upsB var gene promoters carried on episomes are silenced by default, and that promoter activation is sufficient to silence all other family members. However, they are active by default when placed downstream of a second active var promoter, underscoring the significance of local chromatin environment and nuclear compartmentalization in var promoter regulation. Native chromatin covering the SPE2-repeat array in upsB promoters is resistant to nuclease digestion, and insertion of these regulatory elements into a heterologous promoter causes local alterations in nucleosomal organization and promoter repression. Our findings suggest a common logic underlying the transcriptional control of all var genes, and have important implications for our understanding of the epigenetic processes involved in the regulation of this major virulence gene family.
authors.affiliation: Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia.
authors.forename: Till S
authors.initials: TS
authors.lastname: Voss
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Tonkin
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Marty
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Thompson
authors.forename: Julie
authors.initials: J
authors.lastname: Healer
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D010957:Plasmids / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000096:biosynthesis*; D016053:RNA, Protozoan / Q000096:biosynthesis
chemical_list: D002843:Chromatin; D015800:Protozoan Proteins; D016053:RNA, Protozoan; C085731:erythrocyte membrane protein 1, Plasmodium falciparum