Authors

B J Power¹; H J Vaikkinen¹; R S Kent¹; N Philip¹; A P Waters¹;  ¹ University of Glasgow, Institute of Infection, Immunity & Inflammation,, UK

Discussion

According to the World Health Organisation (WHO), 2015 saw 212 million new cases of malaria and 429,000 deaths attributed to malaria worldwide. Five species of the Plasmodium genus are responsible for malaria in humans, of which P. falciparum is the most lethal. In P. falciparum, it has been shown that the epigenetic regulators, heterochromatin protein 1 (PfHP1) and histone deacetylase 2 (PfHDAC2), are essential for both mitotic proliferation of asexual stage malaria parasites and the transition from asexual to sexual stage parasites (gametocytogenesis) required for transmission to the mosquito vector.

In this study, we investigated the epigenetic regulation of commitment to gametocytogenesis, using the rodent malaria model, P. berghei. We employed both gene knockout and conditional auxin-induced knockdown of proteins involved in the acetylation and deacetylation of histones with successful knockout of putative histone deacetylase 1 (HDA1) and histone acetyltransferase 1 (HAT1). Auxin-inducible knockdowns were created for HDA1 and three additional histone deacetylases in P. berghei.

In addition, we have identified both conserved and stage-specific histone modifications for mature synchronous asexual parasites (schizonts) and sexual-stage parasites (gametocytes). Our current work focusses on the identification of chromatin regions demarcated by the stage-specific histone modifications H4K8Ac, H3K122Ac, and H3K64Ac.