Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes
ABSTRACT The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes (CVGs) is associated with euchromatin characterized by the histone m...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-02-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.03049-22 |
| _version_ | 1811164426178396160 |
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| author | Lucas Michel-Todó Cristina Bancells Núria Casas-Vila Núria Rovira-Graells Carles Hernández-Ferrer Juan R. González Alfred Cortés |
| author_facet | Lucas Michel-Todó Cristina Bancells Núria Casas-Vila Núria Rovira-Graells Carles Hernández-Ferrer Juan R. González Alfred Cortés |
| author_sort | Lucas Michel-Todó |
| collection | DOAJ |
| description | ABSTRACT The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes (CVGs) is associated with euchromatin characterized by the histone mark H3K9ac, whereas the silenced state is characterized by H3K9me3-based heterochromatin. Expression switches are linked to euchromatin-heterochromatin transitions, but these transitions have not been characterized for the majority of CVGs. To define the heterochromatin distribution patterns associated with the alternative transcriptional states of CVGs, we compared H3K9me3 occupancy at a genome-wide level among several parasite subclones of the same genetic background that differed in the transcriptional state of many CVGs. We found that de novo heterochromatin formation or the complete disruption of a heterochromatin domain is a relatively rare event, and for the majority of CVGs, expression switches can be explained by the expansion or retraction of heterochromatin domains. We identified different modalities of heterochromatin changes linked to transcriptional differences, but despite this complexity, heterochromatin distribution patterns generally enable the prediction of the transcriptional state of specific CVGs. We also found that in some subclones, several var genes were simultaneously in an active state. Furthermore, the heterochromatin levels in the putative regulatory region of the gdv1 antisense noncoding RNA, a regulator of sexual commitment, varied between parasite lines with different sexual conversion rates. IMPORTANCE The malaria parasite P. falciparum is responsible for more than half a million deaths every year. P. falciparum clonally variant genes (CVGs) mediate fundamental host-parasite interactions and play a key role in parasite adaptation to fluctuations in the conditions of the human host. The expression of CVGs is regulated at the epigenetic level by changes in the distribution of a type of chromatin called heterochromatin. Here, we describe at a genome-wide level the changes in the heterochromatin distribution associated with the different transcriptional states of CVGs. Our results also reveal a likely role for heterochromatin at a particular locus in determining the parasite investment in transmission to mosquitoes. Additionally, this data set will enable the prediction of the transcriptional state of CVGs from epigenomic data, which is important for the study of parasite adaptation to the conditions of the host in natural malaria infections. |
| first_indexed | 2024-04-10T15:21:12Z |
| format | Article |
| id | doaj.art-1883072182ba413d8c0acac0fefb459a |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-10T15:21:12Z |
| publishDate | 2023-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-1883072182ba413d8c0acac0fefb459a2023-02-14T14:15:49ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-02-0111110.1128/spectrum.03049-22Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant GenesLucas Michel-Todó0Cristina Bancells1Núria Casas-Vila2Núria Rovira-Graells3Carles Hernández-Ferrer4Juan R. González5Alfred Cortés6ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, SpainISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, SpainISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, SpainISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, SpainISGlobal, Barcelona, Catalonia, SpainISGlobal, Barcelona, Catalonia, SpainISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, SpainABSTRACT The survival of malaria parasites in the changing human blood environment largely depends on their ability to alter gene expression by epigenetic mechanisms. The active state of Plasmodium falciparum clonally variant genes (CVGs) is associated with euchromatin characterized by the histone mark H3K9ac, whereas the silenced state is characterized by H3K9me3-based heterochromatin. Expression switches are linked to euchromatin-heterochromatin transitions, but these transitions have not been characterized for the majority of CVGs. To define the heterochromatin distribution patterns associated with the alternative transcriptional states of CVGs, we compared H3K9me3 occupancy at a genome-wide level among several parasite subclones of the same genetic background that differed in the transcriptional state of many CVGs. We found that de novo heterochromatin formation or the complete disruption of a heterochromatin domain is a relatively rare event, and for the majority of CVGs, expression switches can be explained by the expansion or retraction of heterochromatin domains. We identified different modalities of heterochromatin changes linked to transcriptional differences, but despite this complexity, heterochromatin distribution patterns generally enable the prediction of the transcriptional state of specific CVGs. We also found that in some subclones, several var genes were simultaneously in an active state. Furthermore, the heterochromatin levels in the putative regulatory region of the gdv1 antisense noncoding RNA, a regulator of sexual commitment, varied between parasite lines with different sexual conversion rates. IMPORTANCE The malaria parasite P. falciparum is responsible for more than half a million deaths every year. P. falciparum clonally variant genes (CVGs) mediate fundamental host-parasite interactions and play a key role in parasite adaptation to fluctuations in the conditions of the human host. The expression of CVGs is regulated at the epigenetic level by changes in the distribution of a type of chromatin called heterochromatin. Here, we describe at a genome-wide level the changes in the heterochromatin distribution associated with the different transcriptional states of CVGs. Our results also reveal a likely role for heterochromatin at a particular locus in determining the parasite investment in transmission to mosquitoes. Additionally, this data set will enable the prediction of the transcriptional state of CVGs from epigenomic data, which is important for the study of parasite adaptation to the conditions of the host in natural malaria infections.https://journals.asm.org/doi/10.1128/spectrum.03049-22ChIP-seqH3K9me3Plasmodium falciparumchromatingdv1clonally variant gene expression |
| spellingShingle | Lucas Michel-Todó Cristina Bancells Núria Casas-Vila Núria Rovira-Graells Carles Hernández-Ferrer Juan R. González Alfred Cortés Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes Microbiology Spectrum ChIP-seq H3K9me3 Plasmodium falciparum chromatin gdv1 clonally variant gene expression |
| title | Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes |
| title_full | Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes |
| title_fullStr | Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes |
| title_full_unstemmed | Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes |
| title_short | Patterns of Heterochromatin Transitions Linked to Changes in the Expression of Plasmodium falciparum Clonally Variant Genes |
| title_sort | patterns of heterochromatin transitions linked to changes in the expression of plasmodium falciparum clonally variant genes |
| topic | ChIP-seq H3K9me3 Plasmodium falciparum chromatin gdv1 clonally variant gene expression |
| url | https://journals.asm.org/doi/10.1128/spectrum.03049-22 |
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