Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.

Autor:	Hammam E; Institut Pasteur, 75015 Paris, France.; CNRS ERL9195, 75015 Paris, France.; INSERM U1201, 75015 Paris, France.; Sorbonne Université, Ecole doctorale Complexité du Vivant ED515, F-75005 Paris, France., Ananda G; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA., Sinha A; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore., Scheidig-Benatar C; Institut Pasteur, 75015 Paris, France.; CNRS ERL9195, 75015 Paris, France.; INSERM U1201, 75015 Paris, France., Bohec M; Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, 75005 Paris, France., Preiser PR; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore., Dedon PC; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Scherf A; Institut Pasteur, 75015 Paris, France.; CNRS ERL9195, 75015 Paris, France.; INSERM U1201, 75015 Paris, France., Vembar SS; Institut Pasteur, 75015 Paris, France.; CNRS ERL9195, 75015 Paris, France.; INSERM U1201, 75015 Paris, France.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2020 Jan 10; Vol. 48 (1), pp. 184-199.
DOI:	10.1093/nar/gkz1093
Abstrakt:	DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2-0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01-0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials. (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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