An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum

Scientific Reports
Rafael M MartinsArtur Scherf

Abstract

Variegated surface antigen expression is key to chronic infection and pathogenesis of the human malaria parasite Plasmodium falciparum. This protozoan parasite expresses distinct surface molecules that are encoded by clonally variant gene families such as var, rif and stevor. The molecular mechanisms governing activation of individual members remain ill-defined. To investigate the molecular events of the initial transcriptional activation process we focused on a member of the apicomplexan ApiAP2 transcription factor family predicted to bind to the 5' upstream regions of the var gene family, AP2-exp (PF3D7_1466400). Viable AP2-exp mutant parasites rely on expressing no less than a short truncated protein including the N-terminal AP2 DNA-binding domain. RNA-seq analysis in mutant parasites revealed transcriptional changes in a subset of exported proteins encoded by clonally variant gene families. Upregulation of RIFINs and STEVORs was validated at the protein levels. In addition, morphological alterations were observed on the surface of the host cells infected by the mutants. This work points to a complex regulatory network of clonally variant gene families in which transcription of a subset of members is regulated by the same tr...Continue Reading

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Citations

Jan 29, 2019·Genome Biology and Evolution·Andreina I CastilloEric Lyons
Jun 21, 2019·Briefings in Functional Genomics·Christa G Toenhake, Richárd Bártfai
Aug 21, 2020·Molecular Systems Biology·Jessica M BryantArtur Scherf
Jul 18, 2018·Nucleic Acids Research·José Luis RuizElena Gómez-Díaz
Apr 10, 2019·Pathogens·Myriam D JeningaMichaela Petter
Jun 21, 2018·Scientific Reports·Rosana Beatriz Duque AraujoGerhard Wunderlich
May 7, 2019·Briefings in Functional Genomics·José L Ruiz, Elena Gómez-Díaz
Jan 12, 2021·Frontiers in Cellular and Infection Microbiology·Thomas Hollin, Karine G Le Roch
Mar 17, 2021·International Journal for Parasitology·H A Walters, L A Temesvari
Jul 17, 2021·Frontiers in Cellular and Infection Microbiology·Eliana F G CubillosGerhard Wunderlich

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Datasets Mentioned

BETA
PRJEB20833

Methods Mentioned

BETA
PCR
gene knockout
flow cytometry
RNA-seq
Scanning electron microscopy
IEC
ChIP
acetylation
ChIP-seq
pull downs

Software Mentioned

R
FastQC
AP2
BWA MEM
exp

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