title: A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression.
abstract: During red-blood-cell-stage infection of Plasmodium falciparum, the parasite undergoes repeated rounds of replication, egress, and invasion. Erythrocyte invasion involves specific interactions between host cell receptors and parasite ligands and coordinated expression of genes specific to this step of the life cycle. We show that a parasite-specific bromodomain protein, PfBDP1, binds to chromatin at transcriptional start sites of invasion-related genes and directly controls their expression. Conditional PfBDP1 knockdown causes a dramatic defect in parasite invasion and growth and results in transcriptional downregulation of multiple invasion-related genes at a time point critical for invasion. Conversely, PfBDP1 overexpression enhances expression of these same invasion-related genes. PfBDP1 binds to acetylated histone H3 and a second bromodomain protein, PfBDP2, suggesting a potential mechanism for gene recognition and control. Collectively, these findings show that PfBDP1 critically coordinates expression of invasion genes and indicate that targeting PfBDP1 could be an invaluable tool in malaria eradication.
authors.affiliation: Department of Medicine Royal Melbourne Hospital, The Peter Doherty Institute, The University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: Josling
authors.affiliation: Department of Medicine Royal Melbourne Hospital, The Peter Doherty Institute, The University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
authors.forename: Michaela
authors.initials: M
authors.lastname: Petter
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: Sophie C
authors.initials: SC
authors.lastname: Oehring
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551.
authors.forename: Archna P
authors.initials: AP
authors.lastname: Gupta
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: Olivier
authors.initials: O
authors.lastname: Dietz
authors.affiliation: School of Molecular and Biomedical Science, The University of Adelaide, South Australia 5005, Australia; Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Danny W
authors.initials: DW
authors.lastname: Wilson
authors.affiliation: 2bind GmbH, Josef Engert Straße 13, 93053 Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schubert
authors.affiliation: Institute for Biochemistry III, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Längst
authors.affiliation: Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gilson
authors.affiliation: Department of Medicine Royal Melbourne Hospital, The Peter Doherty Institute, The University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Brendan S
authors.initials: BS
authors.lastname: Crabb
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland.
authors.forename: Suzette
authors.initials: S
authors.lastname: Moes
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Jenoe
authors.affiliation: Department of Medicine Royal Melbourne Hospital, The Peter Doherty Institute, The University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia.
authors.forename: Shu Wei
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Department of Medicine Royal Melbourne Hospital, The Peter Doherty Institute, The University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia; Nossal Institute for Global Health, The University of Melbourne, 161 Barry Street, Carlton, Victoria 3010, Australia.
authors.forename: Graham V
authors.initials: GV
authors.lastname: Brown
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551.
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
authors.affiliation: Department of Medicine Royal Melbourne Hospital, The Peter Doherty Institute, The University of Melbourne, 792 Elizabeth Street, Melbourne, Victoria 3000, Australia. Electronic address: mduffy@unimelb.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Duffy
mesh_terms: D000107:Acetylation; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006790:Host-Parasite Interactions; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity*; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D015800:Protozoan Proteins