PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum
The environmental challenges the human malaria parasite, Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DN...
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/92499 |
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| author | Zeinab M Chahine Mohit Gupta Todd Lenz Thomas Hollin Steven Abel Charles Banks Anita Saraf Jacques Prudhomme Suhani Bhanvadia Laurence A Florens Karine G Le Roch |
| author_facet | Zeinab M Chahine Mohit Gupta Todd Lenz Thomas Hollin Steven Abel Charles Banks Anita Saraf Jacques Prudhomme Suhani Bhanvadia Laurence A Florens Karine G Le Roch |
| author_sort | Zeinab M Chahine |
| collection | DOAJ |
| description | The environmental challenges the human malaria parasite, Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. 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 PfMORC 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 PfMORC 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 PfMORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that PfMORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies. |
| format | Article |
| id | doaj-art-c10e0308b5df414d931a2bef7a3a599c |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-c10e0308b5df414d931a2bef7a3a599c2025-08-20T02:19:07ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011210.7554/eLife.92499PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparumZeinab M Chahine0https://orcid.org/0000-0001-8208-5869Mohit Gupta1Todd Lenz2Thomas Hollin3https://orcid.org/0000-0002-8089-3253Steven Abel4Charles Banks5Anita Saraf6https://orcid.org/0000-0001-6756-0975Jacques Prudhomme7https://orcid.org/0000-0002-6161-5194Suhani Bhanvadia8Laurence A Florens9https://orcid.org/0000-0002-9310-6650Karine G Le Roch10https://orcid.org/0000-0002-4862-9292Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesStowers Institute for Medical Research, Kansas City, United StatesStowers Institute for Medical Research, Kansas City, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesStowers Institute for Medical Research, Kansas City, United StatesDepartment of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, United StatesThe environmental challenges the human malaria parasite, Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. 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 PfMORC 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 PfMORC 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 PfMORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm that PfMORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies.https://elifesciences.org/articles/92499malariaepigeneticchromatingene regulation |
| spellingShingle | Zeinab M Chahine Mohit Gupta Todd Lenz Thomas Hollin Steven Abel Charles Banks Anita Saraf Jacques Prudhomme Suhani Bhanvadia Laurence A Florens Karine G Le Roch PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum eLife malaria epigenetic chromatin gene regulation |
| title | PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum |
| title_full | PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum |
| title_fullStr | PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum |
| title_full_unstemmed | PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum |
| title_short | PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite, Plasmodium falciparum |
| title_sort | pfmorc protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite plasmodium falciparum |
| topic | malaria epigenetic chromatin gene regulation |
| url | https://elifesciences.org/articles/92499 |
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