Authors

S Millar¹; J Martin¹; KR Hughes¹; R Morton¹; F Khaliq¹; JB Power¹; D Beraldi¹; AP Waters¹;  ¹ Wellcome Centre for Integrative Parasitology (WCIP), School of Infection & Immunity, University of Glasgow, UK

Discussion

In order for Plasmodium species to transmit to a mosquito vector they must transition from an asexual parasite of the erythrocytic cycle into a sexual male or female gametocyte. Epigenetically regulated expression of ap2-g, a member of the AP2 family of transcription factors was identified as orchestrating this developmental change, guiding the parasite through gametocytogenesis. Although some epigenetic actors controlling ap2-g expression and thus commitment have been identified the full extent of epigenetic regulation remains unclear. Histone Deacetylase 1 (hda1) has previously been shown to be upregulated in P. falciparum following  upregulation of ap2-g, suggesting a role in gametocyte development or function.To investigate the role of HDA1 in both the sexual and asexual life cycle of the rodent malaria species Plasmodium berghei, we generated hda1^- knockout and hda1::gfp tagged lines. Analysis of the knockout by flow cytometry revealed a complex phenotype of slow growth and altered sex ratio. Further investigations using imaging flow cytometry revealed a defect in male exflagellation, which resulted in an absence of ookinetes in the knockout. Transcriptomic and chromatin accessibility studies on sorted male, female and schizont hda1^- populations identified an upregulation of variant gene family members. Analysis of the hda1::gfp line revealed a punctate nuclear HDA1 signal distinct from the DAPI and H3K9me3  signal, suggesting a role in chromatin regulation. In summary, HDA1 plays a key role in gametocyte commitment and emergence.