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© Research
Publication : Scientific reports

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Scientific reports - 25 Oct 2017

Martins RM, Macpherson CR, Claes A, Scheidig-Benatar C, Sakamoto H, Yam XY, Preiser P, Goel S, Wahlgren M, Sismeiro O, Coppée JY, Scherf A

Link to Pubmed [PMID] – 29070841

Sci Rep 2017 Oct;7(1):14042

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 transcription factor. In addition, we highlight the importance of the non-DNA binding AP2 domain in functional gene regulation.

https://www.ncbi.nlm.nih.gov/pubmed/29070841