Proteomics,Multiomics

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A knockout screen of ApiAP2 genes reveals networks of interacting transcriptional regulators controlling the Plasmodium life cycle.


ABSTRACT: The family of apicomplexa-specific proteins with DNA binding AP2 domains (ApiAP2s) includes sequence-specific transcription factors that are key regulators of development in malaria parasites. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identifies ten ApiAP2 genes essential for mosquito transmission, of which four are critical for the formation of infectious ookinetes and three for sporogony. We describe unexpected non-essential functions for AP2-O and AP2-SP proteins in blood stages and identify AP2-G2 as a universal repressor active in both, asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages reveals clusters of co-regulated genes with shared cis elements in their promoters, whose expression can be controlled positively or negatively by different ApiAP2 gene deletions. 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.

OTHER RELATED OMICS DATASETS IN: PRJNA319543

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Plasmodium Berghei

DISEASE(S): Malaria

SUBMITTER: James Wright  

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD005180 | Pride | 2017-02-08

REPOSITORIES: Pride

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Publications

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

Modrzynska Katarzyna K   Pfander Claudia C   Chappell Lia L   Yu Lu L   Suarez Catherine C   Dundas Kirsten K   Gomes Ana Rita AR   Goulding David D   Rayner Julian C JC   Choudhary Jyoti J   Billker Oliver O  

Cell host & microbe 20170101 1


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 wer  ...[more]

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