The Role of the Histone Methyltransferase PfSET10 in Antigenic Variation by Malaria Parasites: a Cautionary Tale.

TitleThe Role of the Histone Methyltransferase PfSET10 in Antigenic Variation by Malaria Parasites: a Cautionary Tale.
Publication TypeJournal Article
Year of Publication2021
AuthorsNgwa CJ, Gross MR, Musabyimana J-P, Pradel G, Deitsch KW
JournalmSphere
Volume6
Issue1
Date Published2021 Feb 03
ISSN2379-5042
KeywordsAntigenic Variation, Antigens, Protozoan, Chromatin, Epigenesis, Genetic, Gene Expression Regulation, Histone Methyltransferases, Plasmodium falciparum, Protozoan Proteins, Transcriptional Activation
Abstract

The virulence of the malaria parasite Plasmodium falciparum is due in large part to its ability to avoid immune destruction through antigenic variation. This results from changes in expression within the multicopy var gene family that encodes the surface antigen P. falciparum erythrocyte protein one (PfEMP1). Understanding the mechanisms underlying this process has been a high-profile research focus for many years. The histone methyltransferase PfSET10 was previously identified as a key enzyme required both for parasite viability and for regulating var gene expression, thus making it a prominent target for developing antimalarial intervention strategies and the subject of considerable research focus. Here, however, we show that disruption of the gene encoding PfSET10 is not lethal and has no effect on var gene expression, in sharp contrast with previously published reports. The contradictory findings highlight the importance of reevaluating previous conclusions when new technologies become available and suggest the possibility of a previously unappreciated plasticity in epigenetic gene regulation in P. falciparumIMPORTANCE The identification of specific epigenetic regulatory proteins in infectious organisms has become a high-profile research topic and a focus for several drug development initiatives. However, studies that define specific roles for different epigenetic modifiers occasionally report differing results, and we similarly provide evidence regarding the histone methyltransferase PfSET10 that is in stark contrast with previously published results. We believe that the conflicting results, rather than suggesting erroneous conclusions, instead reflect the importance of revisiting previous conclusions using newly developed methodologies, as well as caution in interpreting seemingly contrary results in fields that are known to display considerable plasticity, for example metabolism and epigenetics.

DOI10.1128/mSphere.01217-20
Alternate JournalmSphere
PubMed ID33536326
PubMed Central IDPMC7860991
Grant ListR01 AI052390 / AI / NIAID NIH HHS / United States
R01 AI138499 / AI / NIAID NIH HHS / United States

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