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

TitleRed Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor.
Publication TypeJournal Article
Year of Publication2017
AuthorsSantos, JMendonca, Josling, G, Ross, P, Joshi, P, Orchard, L, Campbell, T, Schieler, A, Cristea, IM, Llinás, M
JournalCell Host Microbe
Volume21
Issue6
Pagination731-741.e10
Date Published2017 Jun 14
ISSN1934-6069
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.

DOI10.1016/j.chom.2017.05.006
Alternate JournalCell Host Microbe
PubMed ID28618269
Grant ListP50 GM071508 / GM / NIGMS NIH HHS / United States
R01 AI076276 / AI / NIAID NIH HHS / United States
R01 AI125565 / AI / NIAID NIH HHS / United States
R01 GM114141 / GM / NIGMS NIH HHS / United States