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A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle
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2017 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 1, p. 11-22Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Cell Press , 2017. Vol. 21, no 1, p. 11-22
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-165841DOI: 10.1016/j.chom.2016.12.003ISI: 000392843900005PubMedID: 28081440OAI: oai:DiVA.org:umu-165841DiVA, id: diva2:1379069
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Wellcome trust, 098051Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-18Bibliographically approved

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