Dataset Information

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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			Action	DRS
	Fusion_KMTMT10RPpH10_P01.raw	Raw
	Fusion_KMTMT10RPpH10_P02X.raw	Raw
	Fusion_KMTMT10RPpH10_P03.raw	Raw
	Fusion_KMTMT10RPpH10_P04.raw	Raw
	Fusion_KMTMT10RPpH10_P05.raw	Raw

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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]

PMID: 28081440

Similar Datasets

Project description:The emerging picture of transcriptional regulation is one of unexpected complexity. It is now clear that single transcription factors control hundreds, if not thousands, of direct targets by binding their genomic loci, but it is not understood how many of these are major players and how many are supporting cast. To address this, we leverage a well-characterized developmental network in Arabidopsis and map genome-wide binding of related proteins in multiple tissues. The transcription factor APETALA2 (AP2) has numerous functions, including roles in floral organ identity, seed development and stem cell maintenance. We focus on the role of AP2 in the floral transition and map direct targets on a genome-wide scale. We show that ap2 mutants flower early in long and short days, and that AP2 binds to many loci, most prominently floral pathway integrators, microRNAs and floral organ identity genes, many of which exhibit AP2-dependent transcription. Opposing, logical effects are evident in AP2 binding to two developmental microRNA genes that control AP2 expression, with AP2 positively regulating miR156 and negatively regulating miR172, forming a complex direct feedback loop, which also included all but one of the AP2-like miR172 target clade members. We also seek conserved targets by comparing the genome-wide direct target repertoire of AP2 with that of SCHLAFMÜTZE (SMZ), another member of the AP2-like miR172 target clade that shares partial redundancy, as evidenced by a hexuple mutant for the entire clade that flowered extremely early. Clear similarities and divergence are exposed in the AP2 and SMZ direct target repertoires. Finally, using an inducible expression system, we demonstrate that AP2 has dual molecular roles. It functions both as a transcriptional activator and repressor, directly inducing the expression of the floral repressor AGAMOUS-LIKE 15 (AGL15), and directly repressing the transcription of floral activators like SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). ChIP-Seq of two biological replicates for ATH-AP2 and respective control samples