title: A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.
abstract: A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. Electronic address: km8@sanger.ac.uk.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Modrzynska
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pfander
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Lia
authors.initials: L
authors.lastname: Chappell
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Suarez
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Dundas
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Gomes
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Choudhary
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. Electronic address: ob4@sanger.ac.uk.
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D016782:Apicomplexa / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D055786:Gene Knockout Techniques; D008018:Life Cycle Stages / Q000235:genetics*; D008288:Malaria / Q000469:parasitology / Q000635:transmission*; D051379:Mice; D033661:Oocysts / Q000166:cytology; D010962:Plasmodium berghei / Q000235:genetics* / Q000254:growth & development; D000072417:Protein Domains / Q000235:genetics* / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D015800:Protozoan Proteins
keywords: Apetala 2; ap2-l; ap2-o; ap2-o2; ap2-o3; ap2-o4; ap2-sp; ap2-sp2; ap2-sp3; oocyst