APlasmodium falciparumMORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin

Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasitePlasmodium falciparum. We show thatPfMORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (AP2) transcription factors (PfAP2-G5,PfAP2-O5,PfAP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (PfCHD1 andPfEELM2). Transcriptomic analysis ofPfMORC^HA-glmSknockdown parasites revealed 163 differentially expressed genes belonging to hypervariable multigene families, along with upregulation of genes mostly involved in host cell invasion.In vivogenome-wide chromatin occupancy analysis during both trophozoite and schizont stages of development demonstrates thatPfMORC is recruited to repressed, multigene families, including thevargenes in subtelomeric chromosomal regions. Collectively, we find thatPfMORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.