Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites
Abstract Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the rin...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13072-023-00500-y |
| _version_ | 1797801253456052224 |
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| author | Ashley B. Reers Rodriel Bautista James McLellan Beatriz Morales Rolando Garza Sebastiaan Bol Kirsten K. Hanson Evelien M. Bunnik |
| author_facet | Ashley B. Reers Rodriel Bautista James McLellan Beatriz Morales Rolando Garza Sebastiaan Bol Kirsten K. Hanson Evelien M. Bunnik |
| author_sort | Ashley B. Reers |
| collection | DOAJ |
| description | Abstract Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology. Here, we sought to characterize gene expression and the corresponding histone PTM landscape during this stage of the parasite lifecycle through RNA-seq and ChIP-seq on P. falciparum blood stage schizonts, merozoites, and rings, as well as P. berghei liver stage merozoites. In both hepatic and erythrocytic merozoites, we identified a subset of genes with a unique histone PTM profile characterized by a region of H3K4me3 depletion in their promoter. These genes were upregulated in hepatic and erythrocytic merozoites and rings, had roles in protein export, translation, and host cell remodeling, and shared a DNA motif. These results indicate that similar regulatory mechanisms may underlie merozoite formation in the liver and blood stages. We also observed that H3K4me2 was deposited in gene bodies of gene families encoding variant surface antigens in erythrocytic merozoites, which may facilitate switching of gene expression between different members of these families. Finally, H3K18me and H2K27me were uncoupled from gene expression and were enriched around the centromeres in erythrocytic schizonts and merozoites, suggesting potential roles in the maintenance of chromosomal organization during schizogony. Together, our results demonstrate that extensive changes in gene expression and histone landscape occur during the schizont-to-ring transition to facilitate productive erythrocyte infection. The dynamic remodeling of the transcriptional program in hepatic and erythrocytic merozoites makes this stage attractive as a target for novel anti-malarial drugs that may have activity against both the liver and blood stages. |
| first_indexed | 2024-03-13T04:47:39Z |
| format | Article |
| id | doaj.art-9b04afded5d5497284cef94c137dfba6 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-03-13T04:47:39Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-9b04afded5d5497284cef94c137dfba62023-06-18T11:25:12ZengBMCEpigenetics & Chromatin1756-89352023-06-0116112510.1186/s13072-023-00500-yHistone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasitesAshley B. Reers0Rodriel Bautista1James McLellan2Beatriz Morales3Rolando Garza4Sebastiaan Bol5Kirsten K. Hanson6Evelien M. Bunnik7Department of Microbiology, Immunology, and Molecular Genetics, Long School of Medicine, University of Texas Health Science CenterDepartment of Microbiology, Immunology, and Molecular Genetics, Long School of Medicine, University of Texas Health Science CenterDepartment of Molecular Microbiology and Immunology and South Texas Center for Emerging Infectious Diseases, University of Texas San AntonioDepartment of Molecular Microbiology and Immunology and South Texas Center for Emerging Infectious Diseases, University of Texas San AntonioDepartment of Microbiology, Immunology, and Molecular Genetics, Long School of Medicine, University of Texas Health Science CenterDepartment of Microbiology, Immunology, and Molecular Genetics, Long School of Medicine, University of Texas Health Science CenterDepartment of Molecular Microbiology and Immunology and South Texas Center for Emerging Infectious Diseases, University of Texas San AntonioDepartment of Microbiology, Immunology, and Molecular Genetics, Long School of Medicine, University of Texas Health Science CenterAbstract Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology. Here, we sought to characterize gene expression and the corresponding histone PTM landscape during this stage of the parasite lifecycle through RNA-seq and ChIP-seq on P. falciparum blood stage schizonts, merozoites, and rings, as well as P. berghei liver stage merozoites. In both hepatic and erythrocytic merozoites, we identified a subset of genes with a unique histone PTM profile characterized by a region of H3K4me3 depletion in their promoter. These genes were upregulated in hepatic and erythrocytic merozoites and rings, had roles in protein export, translation, and host cell remodeling, and shared a DNA motif. These results indicate that similar regulatory mechanisms may underlie merozoite formation in the liver and blood stages. We also observed that H3K4me2 was deposited in gene bodies of gene families encoding variant surface antigens in erythrocytic merozoites, which may facilitate switching of gene expression between different members of these families. Finally, H3K18me and H2K27me were uncoupled from gene expression and were enriched around the centromeres in erythrocytic schizonts and merozoites, suggesting potential roles in the maintenance of chromosomal organization during schizogony. Together, our results demonstrate that extensive changes in gene expression and histone landscape occur during the schizont-to-ring transition to facilitate productive erythrocyte infection. The dynamic remodeling of the transcriptional program in hepatic and erythrocytic merozoites makes this stage attractive as a target for novel anti-malarial drugs that may have activity against both the liver and blood stages.https://doi.org/10.1186/s13072-023-00500-yMalariaEpigeneticsGene regulationTranscriptomicsChromatin immunoprecipitation |
| spellingShingle | Ashley B. Reers Rodriel Bautista James McLellan Beatriz Morales Rolando Garza Sebastiaan Bol Kirsten K. Hanson Evelien M. Bunnik Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites Epigenetics & Chromatin Malaria Epigenetics Gene regulation Transcriptomics Chromatin immunoprecipitation |
| title | Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites |
| title_full | Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites |
| title_fullStr | Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites |
| title_full_unstemmed | Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites |
| title_short | Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites |
| title_sort | histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of plasmodium parasites |
| topic | Malaria Epigenetics Gene regulation Transcriptomics Chromatin immunoprecipitation |
| url | https://doi.org/10.1186/s13072-023-00500-y |
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