Histone Lactylation Dynamics in Plasmodium falciparum

Abstract

Epigenetic modifications of the histone are a rapidly unfolding field of research with new posttranslational modifications being uncovered at a rapid pace. Histone lactylation is a newly identified modification associated with metabolism and it has been shown to exist in various organisms including humans and parasites. In some organisms it has shown dynamic changes with response to environmental changes, suggesting a possible mechanism of regulating gene expression profiles in response to environmental factors. In Plasmodium falciparum severe infections have a direct impact on environmental conditions, including blood lactate levels. This investigation demonstrates a responsiveness to histone lactylation in Plasmodium falciparum at each stage of the intra-erythrocytic development cycle in response to increases in environmental lactate. Additionally, examination of readers and writers of other epigenetic markers led to the investigation of Sirtuin proteins as potential erasers of histone lactylation. Knocking out Sirtuin proteins demonstrates increases in histone lactylation that indicates involvement in the removal of lactate signal from histone proteins.