Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor

Joana Mendonca Santos, Gabrielle Josling, Philipp Ross, Preeti Joshi, Lindsey Orchard, Tracey Campbell, Ariel Schieler, Ileana M. Cristea, Manuel Llinás

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes. Although PfAP2-I contains three AP2 DNA-binding domains, only one is required for binding of the target genes during blood stage development. Furthermore, we find that PfAP2-I associates with several chromatin-associated proteins, including the Plasmodium bromodomain protein PfBDP1 and that complex formation is associated with transcriptional regulation. As a key regulator of red blood cell invasion, PfAP2-I represents a potential new antimalarial therapeutic target.

Original languageEnglish (US)
Pages (from-to)731-741.e10
JournalCell Host and Microbe
Volume21
Issue number6
DOIs
StatePublished - Jun 14 2017

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Malaria
Parasites
Transcription Factors
Erythrocytes
Nucleotide Motifs
Plasmodium
Falciparum Malaria
Antimalarials
Genes
Chromatin
Proteins
Genome
Gene Expression
DNA
Therapeutics
multicatalytic protease activator

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Cite this

Santos, Joana Mendonca ; Josling, Gabrielle ; Ross, Philipp ; Joshi, Preeti ; Orchard, Lindsey ; Campbell, Tracey ; Schieler, Ariel ; Cristea, Ileana M. ; Llinás, Manuel. / Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor. In: Cell Host and Microbe. 2017 ; Vol. 21, No. 6. pp. 731-741.e10.
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Santos, JM, Josling, G, Ross, P, Joshi, P, Orchard, L, Campbell, T, Schieler, A, Cristea, IM & Llinás, M 2017, 'Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor', Cell Host and Microbe, vol. 21, no. 6, pp. 731-741.e10. https://doi.org/10.1016/j.chom.2017.05.006

Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor. / Santos, Joana Mendonca; Josling, Gabrielle; Ross, Philipp; Joshi, Preeti; Orchard, Lindsey; Campbell, Tracey; Schieler, Ariel; Cristea, Ileana M.; Llinás, Manuel.

In: Cell Host and Microbe, Vol. 21, No. 6, 14.06.2017, p. 731-741.e10.

Research output: Contribution to journalArticle

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AU - Santos, Joana Mendonca

AU - Josling, Gabrielle

AU - Ross, Philipp

AU - Joshi, Preeti

AU - Orchard, Lindsey

AU - Campbell, Tracey

AU - Schieler, Ariel

AU - Cristea, Ileana M.

AU - Llinás, Manuel

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AB - Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes. Although PfAP2-I contains three AP2 DNA-binding domains, only one is required for binding of the target genes during blood stage development. Furthermore, we find that PfAP2-I associates with several chromatin-associated proteins, including the Plasmodium bromodomain protein PfBDP1 and that complex formation is associated with transcriptional regulation. As a key regulator of red blood cell invasion, PfAP2-I represents a potential new antimalarial therapeutic target.

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