@article{487f58bfc3364cd1a713cdf8bfa5c0ef,
title = "Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor",
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.",
keywords = "ApiAP2 protein, ChIP-seq, DNA motif, Plasmodium falciparum, gene expression, host cell invasion, malaria, parasite, transcription factor, transcriptional regulation",
author = "Santos, {Joana Mendonca} and Gabrielle Josling and Philipp Ross and Preeti Joshi and Lindsey Orchard and Tracey Campbell and Ariel Schieler and Cristea, {Ileana M.} and Manuel Llin{\'a}s",
note = "Funding Information: J.M.S. is a recipient of Swiss National Fund GEP3-13613 and EMBO Long-Term Fellowship 633-2011, T.L.C. was funded by an NSERC Postdoctoral Fellowship, J.P. was funded by an NJCCR postdoctoral fellowship, and G.J. is the recipient of an American Heart Association Postdoctoral Research Grant 16POST26420067. This work was funded by NIH/NIAID R01AI076276 (M.L.) and R01AI125565 (M.L.), the Arnold and Mabel Beckman Foundation (002375), and support from the Center for Quantitative Biology (P50 GM071508) (M.L.) and R01GM114141 (I.M.C.). We thank the Voss (SIP2N-HA), Cowman (CHD1-GFP), and Duffy (BDP1-HA) labs for sharing parasite strains. We thank Dr. T. Greco in the Cristea lab for the mass spectrometric analysis at Princeton University and Dr. T. Laremore for those performed at the Pennsylvania State University in the Huck Proteomics and Mass Spectrometry Core Facility. We thank Dr. T. Otto, Dr. M. Berriman, and Dr. U. Boehme from the UK Wellcome Trust Sanger Institute for use of the Pf Dd2 draft annotations from the Pf3K project. We thank Dr. H. Painter for help with Rnits, discussions of the data, and critical reading of the manuscript. We thank A. Minns for assistance with protein quantification. High-throughput sequencing analyses were performed at the Huck Genomics Core Facility, University Park, PA. The anti-MSP4 and anti-MSP5 antibodies were obtained through the MR4 as part of the BEI resources repository. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jun,
day = "14",
doi = "10.1016/j.chom.2017.05.006",
language = "English (US)",
volume = "21",
pages = "731--741.e10",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "6",
}