A <i>Plasmodium falciparum</i> MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin.

Abstract

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 parasite <i>Plasmodium falciparum</i>. We show that <i>Pf</i>MORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (ApiAP2) transcription factors (<i>Pf</i>AP2-G5, <i>Pf</i>AP2-O5, <i>Pf</i>AP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (<i>Pf</i>CHD1 and <i>Pf</i>EELM2). Transcriptomic analysis of <i>Pf</i>MORC^HA-glmS knockdown parasites revealed 163 differentially expressed genes belonging to hypervariable multigene families, along with upregulation of genes mostly involved in host cell invasion. In vivo genome-wide chromatin occupancy analysis during both trophozoite and schizont stages of development demonstrates that <i>Pf</i>MORC is recruited to repressed, multigene families, including the <i>var</i> genes in subtelomeric chromosomal regions. Collectively, we find that <i>Pf</i>MORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.