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Cell Host Microbe. 2017 Jan 11;21(1):11-22. doi: 10.1016/j.chom.2016.12.003.

A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.

Author information

1
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. Electronic address: km8@sanger.ac.uk.
2
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
3
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK. Electronic address: ob4@sanger.ac.uk.

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.

KEYWORDS:

Apetala 2; ap2-l; ap2-o; ap2-o2; ap2-o3; ap2-o4; ap2-sp; ap2-sp2; ap2-sp3; oocyst

PMID:
28081440
PMCID:
PMC5241200
DOI:
10.1016/j.chom.2016.12.003
[Indexed for MEDLINE]
Free PMC Article

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