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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\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    . We show that\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (ApiAP2) transcription factors (\n                    <jats:italic>Pf<\/jats:italic>\n                    AP2-G5,\n                    <jats:italic>Pf<\/jats:italic>\n                    AP2-O5,\n                    <jats:italic>Pf<\/jats:italic>\n                    AP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (\n                    <jats:italic>Pf<\/jats:italic>\n                    CHD1 and\n                    <jats:italic>Pf<\/jats:italic>\n                    EELM2). Transcriptomic analysis of\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC\n                    <jats:sup>HA-glmS<\/jats:sup>\n                    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\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC is recruited to repressed, multigene families, including the\n                    <jats:italic>var<\/jats:italic>\n                    genes in subtelomeric chromosomal regions. Collectively, we find that\n                    <jats:italic>Pf<\/jats:italic>\n                    MORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.\n                  <\/jats:p>","DOI":"10.7554\/elife.92201","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T09:53:12Z","timestamp":1700128392000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92201","source":"Crossref","is-referenced-by-count":7,"title":["A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1474-4695","authenticated-orcid":true,"given":"Maneesh Kumar","family":"Singh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02k5swt12","id-type":"ROR","asserted-by":"publisher"}],"name":"Department 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