PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, P. falciparum

Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing and accumulating evidence has exposed a possible role the MORC protein plays as a transcriptional switch in apicomplexan parasites. Using CRISPR/Cas9 genome editing with complementary molecular and genomics approaches, we demonstrated that PfMORC does not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggest that PfMORC binds to all sub-telomeric regions and internal var genes, and is also likely a key modulator of major stage transitions. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies also indicate that downregulation of PfMORC induces the collapse of the parasite heterochromatin that leads to its death. These findings confirm that PfMORC regulates chromatin structure and gene expression, but also validate this factor as a strong candidate for novel antimalarial strategies.