Modrzynska, K. et al. (2017) A knockout screen of ApiAP2 genes reveals networks of interacting transcriptional regulators controlling the Plasmodium life cycle. Cell Host and Microbe, 21(1), pp. 11-22. (doi: 10.1016/j.chom.2016.12.003) (PMID:28081440) (PMCID:PMC5241200)
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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.
| Item Type: | Articles |
|---|---|
| Additional Information: | Work at the Sanger Institute was funded by grants from the Wellcome Trust (098051) and the Medical Research Council (G0501670). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Modrzynska, Dr Katarzyna |
| Authors: | Modrzynska, K., Pfander, C., Chappell, L., Yu, L., Suarez, C., Dundas, K., Gomes, A. R., Goulding, D., Rayner, J. C., Choudhary, J., and Billker, O. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Cell Host and Microbe |
| Publisher: | Elsevier |
| ISSN: | 1931-3128 |
| ISSN (Online): | 1934-6069 |
| Published Online: | 11 January 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Cell Host and Microbe 21(1):11-22 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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