A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin
A Plasmodium falciparum 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 Plasmodium falciparum. We show that PfMORC (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 and PfEELM2). Transcriptomic analysis of PfMORCHA-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 PfMORC is recruited to repressed, multigene families, including the var genes in subtelomeric chromosomal regions. Collectively, we find that PfMORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.
Palmisano Giuseppe、Moraes Miriam S.、Bonnell Victoria A.、Garcia C¨|lia R. S.、Santiago Ver?nica Feijoli、Da Silva Israel Tojal、Singh Maneesh Kumar、Adderley Jack、Doerig Christian、Llin¨￠s Manuel
Department of Parasitology, Institute of Biomedical Science, University of S?o PauloDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S?o PauloDepartment of Biochemistry and Molecular Biology, Pennsylvania State University, University Park||Huck Institutes Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park||Huck Institutes Center for Malaria Research, Pennsylvania State University, University ParkDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S?o PauloDepartment of Parasitology, Institute of Biomedical Science, University of S?o PauloHospital AC Camargo, Centro Internacional de PesquisaDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S?o PauloSchool of Health and Biomedical Sciences, RMIT UniversitySchool of Health and Biomedical Sciences, RMIT UniversityDepartment of Biochemistry and Molecular Biology, Pennsylvania State University, University Park||Huck Institutes Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park||Huck Institutes Center for Malaria Research, Pennsylvania State University, University Park||Department of Chemistry, Pennsylvania State University, University Park
基础医学分子生物学生物科学研究方法、生物科学研究技术
Palmisano Giuseppe,Moraes Miriam S.,Bonnell Victoria A.,Garcia C¨|lia R. S.,Santiago Ver?nica Feijoli,Da Silva Israel Tojal,Singh Maneesh Kumar,Adderley Jack,Doerig Christian,Llin¨￠s Manuel.A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2023.09.11.557196.点此复制
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