title: Genome-wide mapping of DNA methylation in the human malaria parasite Plasmodium falciparum.
abstract: Cytosine DNA methylation is an epigenetic mark in most eukaryotic cells that regulates numerous processes, including gene expression and stress responses. We performed a genome-wide analysis of DNA methylation in the human malaria parasite Plasmodium falciparum. We mapped the positions of methylated cytosines and identified a single functional DNA methyltransferase (Plasmodium falciparum DNA methyltransferase; PfDNMT) that may mediate these genomic modifications. These analyses revealed that the malaria genome is asymmetrically methylated and shares common features with undifferentiated plant and mammalian cells. Notably, core promoters are hypomethylated, and transcript levels correlate with intraexonic methylation. Additionally, there are sharp methylation transitions at nucleosome and exon-intron boundaries. These data suggest that DNA methylation could regulate virulence gene expression and transcription elongation. Furthermore, the broad range of action of DNA methylation and the uniqueness of PfDNMT suggest that the methylation pathway is a potential target for antimalarial strategies.
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA; INRA, UR1264-MycSA, 71 Avenue E. Bourlaux, CS20032, 33882 Villenave d'Ornon Cedex, France.
authors: Nadia
authors: N
authors: Ponts
authors: Department of Chemistry, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Lijuan
authors: L
authors: Fu
authors: Department of Computer Science and Engineering, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Elena Y
authors: EY
authors: Harris
authors: Department of Chemistry, University of California, 900 University Avenue, Riverside, CA 92521, USA; School of Chemistry & Materials Science, Shaanxi Normal University, 199 South Chang'an Road, Xi'an 710062, China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Duk-Won D
authors: DW
authors: Chung
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Michael C
authors: MC
authors: Cervantes
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Jacques
authors: J
authors: Prudhomme
authors: INRA, UR1264-MycSA, 71 Avenue E. Bourlaux, CS20032, 33882 Villenave d'Ornon Cedex, France.
authors: Vessela
authors: V
authors: Atanasova-Penichon
authors: INRA, UR1264-MycSA, 71 Avenue E. Bourlaux, CS20032, 33882 Villenave d'Ornon Cedex, France.
authors: Enric
authors: E
authors: Zehraoui
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Evelien M
authors: EM
authors: Bunnik
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Elisandra M
authors: EM
authors: Rodrigues
authors: Department of Computer Science and Engineering, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Stefano
authors: S
authors: Lonardi
authors: Center for Plant Cell Biology and Department of Botany & Plant Sciences, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Glenn R
authors: GR
authors: Hicks
authors: Department of Chemistry, University of California, 900 University Avenue, Riverside, CA 92521, USA.
authors: Yinsheng
authors: Y
authors: Wang
authors: Department of Cell Biology and Neuroscience, University of California, 900 University Avenue, Riverside, CA 92521, USA. Electronic address: karine.leroch@ucr.edu.
authors: Karine G
authors: KG
authors: Le Roch
mesh_terms: D002853:Chromatography, Liquid; D019175:DNA Methylation; D016054:DNA, Protozoan / Q000737:chemistry* / Q000378:metabolism; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D044127:Epigenesis, Genetic; D004912:Erythrocytes / Q000469:parasitology; D018503:Genome, Protozoan; D006801:Humans; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D016054:DNA, Protozoan; D015257:DNA-Cytosine Methylases