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Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light on the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using the CRISPR\/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate that\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggests that\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC binds to not only sub-telomeric regions and genes involved in antigenic variation but may also play a role in modulating stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation of\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies.\n                  <\/jats:p>","DOI":"10.7554\/elife.92499","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T11:49:41Z","timestamp":1700480981000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92499","source":"Crossref","is-referenced-by-count":5,"title":["PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-5869","authenticated-orcid":true,"given":"Zeinab M","family":"Chahine","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03nawhv43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department 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