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

Publication date: 11 January 2017
Source:Cell Host & Microbe, Volume 21, Issue 1
Author(s): Katarzyna Modrzynska, Claudia Pfander, Lia Chappell, Lu Yu, Catherine Suarez, Kirsten Dundas, Ana Rita Gomes, David Goulding, Julian C. Rayner, Jyoti Choudhary, Oliver Billker
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.

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Teaser

Modrzynska et al. investigate 25 putative transcriptional regulators of the apiAP2 family in a malaria parasite using a systematic knockout screen. Cellular and molecular phenotyping of the 11 viable mutants obtained reveals complex interactions between positive and negative regulators controlling the Plasmodium life cycle at different stages.


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