A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.
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ICR Authors
Authors
Modrzynska, K
Pfander, C
Chappell, L
Yu, L
Suarez, C
Dundas, K
Gomes, AR
Goulding, D
Rayner, JC
Choudhary, J
Billker, O
Pfander, C
Chappell, L
Yu, L
Suarez, C
Dundas, K
Gomes, AR
Goulding, D
Rayner, JC
Choudhary, J
Billker, O
Document Type
Journal Article
Date
2017-01-11
Date Accepted
2016-11-17
Date Available
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.
Citation
Cell host & microbe, 2017, 21 (1), pp. 11 - 22
Source Title
Publisher
CELL PRESS
ISSN
1931-3128
eISSN
1934-6069