title: Heterochromatin protein 1 secures survival and transmission of malaria parasites.
abstract: Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Nicolas M B
authors.initials: NMB
authors.lastname: Brancucci
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Bertschi
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Niederwieser
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
authors.forename: Wai Hoe
authors.initials: WH
authors.lastname: Chin
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Rahel
authors.initials: R
authors.lastname: Wampfler
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Freymond
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rottmann
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Bozdech
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland. Electronic address: till.voss@unibas.ch.
authors.forename: Till S
authors.initials: TS
authors.lastname: Voss
mesh_terms: D059447:Cell Cycle Checkpoints; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000635:transmission; D010963:Plasmodium falciparum / Q000166:cytology / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*; D059467:Transcriptome
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D015800:Protozoan Proteins; D000090266:Chromobox Protein Homolog 5