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dc.contributor.authorHammam, Elie
dc.contributor.authorAnanda, Guruprasad
dc.contributor.authorSinha, Ameya
dc.contributor.authorScheidig-Benatar, Christine
dc.contributor.authorBohec, Mylene
dc.contributor.authorPreiser, Peter R
dc.contributor.authorDedon, Peter C
dc.contributor.authorScherf, Artur
dc.contributor.authorVembar, Shruthi S
dc.date.accessioned2020-07-21T14:46:07Z
dc.date.available2020-07-21T14:46:07Z
dc.date.issued2019-11
dc.date.submitted2019-10
dc.identifier.issn0305-1048
dc.identifier.issn1362-4962
dc.identifier.urihttps://hdl.handle.net/1721.1/126273
dc.description.abstractDNA 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.en_US
dc.language.isoen
dc.publisherOxford University Press (OUP)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1093/nar/gkz1093en_US
dc.rightsCreative Commons Attribution NonCommercial License 4.0en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.sourceNucleic Acids Researchen_US
dc.titleDiscovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasitesen_US
dc.typeArticleen_US
dc.identifier.citationHammam, Ellie et al. "Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites." Nucleic Acids Research 48, 1 (November 2019): 184–199 © 2019 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.relation.journalNucleic Acids Researchen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-03-05T17:41:30Z
dspace.date.submission2020-03-05T17:41:32Z
mit.journal.volume48en_US
mit.journal.issue1en_US
mit.licensePUBLISHER_CC


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