TY - JOUR
T1 - Genome-wide mapping of DNA methylation in the human malaria parasite plasmodium falciparum
AU - Ponts, Nadia
AU - Fu, Lijuan
AU - Harris, Elena Y.
AU - Zhang, Jing
AU - Chung, Duk Won D.
AU - Cervantes, Michael C.
AU - Prudhomme, Jacques
AU - Atanasova-Penichon, Vessela
AU - Zehraoui, Enric
AU - Bunnik, Evelien M.
AU - Rodrigues, Elisandra M.
AU - Lonardi, Stefano
AU - Hicks, Glenn R.
AU - Wang, Yinsheng
AU - Le Roch, Karine G.
N1 - Funding Information:
The authors thank Thomas Girke, Tyler Backman, Rebecca Sun, and Barbara Walter (IIGB UC Riverside) for assistance with Illumina sequencing and pipeline analysis. They also thank Dr. Felix Krueger (Babraham Institute, UK) for his expertise and Vance C. Huskins for his attentive proofreading. This study was supported by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health R01AI085077 (K.G.L.R.), R01CA101864 (Y.W.), and T34GM062756; by NSF-CAREER IIS-0447773 (S.L.) and NSF IIS-1302134 (S.L.); and by the Human Frontier Science Program LT000507/2011-L (E.M.B.).
PY - 2013/12/11
Y1 - 2013/12/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84890294626
UR - https://www.scopus.com/pages/publications/84890294626#tab=citedBy
U2 - 10.1016/j.chom.2013.11.007
DO - 10.1016/j.chom.2013.11.007
M3 - Article
C2 - 24331467
AN - SCOPUS:84890294626
SN - 1931-3128
VL - 14
SP - 696
EP - 706
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 6
ER -