Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion
Abstract A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation r...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15518-7 |
| _version_ | 1818162726578421760 |
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| author | Shahin Tajeri Laurence Momeux Benjamin Saintpierre Sara Mfarrej Alexander Chapple Tobias Mourier Brian Shiels Frédéric Ariey Arnab Pain Gordon Langsley |
| author_facet | Shahin Tajeri Laurence Momeux Benjamin Saintpierre Sara Mfarrej Alexander Chapple Tobias Mourier Brian Shiels Frédéric Ariey Arnab Pain Gordon Langsley |
| author_sort | Shahin Tajeri |
| collection | DOAJ |
| description | Abstract A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation regulate developmental stage transition of Theileria annulata, another apicomplexan species. We found that FR235222 treatment of T. annulata-infected transformed leukocytes induced a proliferation arrest. The blockade in proliferation was due to drug-induced conversion of intracellular schizonts to merozoites that lack the ability to maintain host leukocyte cell division. Induction of merogony by FR235222 leads to an increase in expression of merozoite-marker (rhoptry) proteins. RNA-seq of FR235222-treated T. annulata-infected B cells identified deregulated expression of 468 parasite genes including a number encoding parasite ApiAP2 transcription factors. Thus, similar to T. gondii, FR235222 inhibits T. annulata HDAC (TaHDAC1) activity and places parasite histone acetylation as a major regulatory event of the transition from schizonts to merozoites. |
| first_indexed | 2024-12-11T16:38:15Z |
| format | Article |
| id | doaj.art-b9dd82b8dc624f799c5869c9c2809f6c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-11T16:38:15Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b9dd82b8dc624f799c5869c9c2809f6c2022-12-22T00:58:24ZengNature PortfolioScientific Reports2045-23222022-07-0112111110.1038/s41598-022-15518-7Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversionShahin Tajeri0Laurence Momeux1Benjamin Saintpierre2Sara Mfarrej3Alexander Chapple4Tobias Mourier5Brian Shiels6Frédéric Ariey7Arnab Pain8Gordon Langsley9Laboratoire de Biologie Comparative Des Apicomplexes, Faculté de Médecine, Université Paris Descartes – Sorbonne Paris CitéLaboratoire de Biologie Comparative Des Apicomplexes, Faculté de Médecine, Université Paris Descartes – Sorbonne Paris CitéPlateforme Génomique, Institut CochinPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST)Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of GlasgowPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST)Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of GlasgowLaboratoire de Biologie Comparative Des Apicomplexes, Faculté de Médecine, Université Paris Descartes – Sorbonne Paris CitéPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST)Laboratoire de Biologie Comparative Des Apicomplexes, Faculté de Médecine, Université Paris Descartes – Sorbonne Paris CitéAbstract A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation regulate developmental stage transition of Theileria annulata, another apicomplexan species. We found that FR235222 treatment of T. annulata-infected transformed leukocytes induced a proliferation arrest. The blockade in proliferation was due to drug-induced conversion of intracellular schizonts to merozoites that lack the ability to maintain host leukocyte cell division. Induction of merogony by FR235222 leads to an increase in expression of merozoite-marker (rhoptry) proteins. RNA-seq of FR235222-treated T. annulata-infected B cells identified deregulated expression of 468 parasite genes including a number encoding parasite ApiAP2 transcription factors. Thus, similar to T. gondii, FR235222 inhibits T. annulata HDAC (TaHDAC1) activity and places parasite histone acetylation as a major regulatory event of the transition from schizonts to merozoites.https://doi.org/10.1038/s41598-022-15518-7 |
| spellingShingle | Shahin Tajeri Laurence Momeux Benjamin Saintpierre Sara Mfarrej Alexander Chapple Tobias Mourier Brian Shiels Frédéric Ariey Arnab Pain Gordon Langsley Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion Scientific Reports |
| title | Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion |
| title_full | Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion |
| title_fullStr | Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion |
| title_full_unstemmed | Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion |
| title_short | Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion |
| title_sort | theileria annulata histone deacetylase 1 tahdac1 initiates schizont to merozoite stage conversion |
| url | https://doi.org/10.1038/s41598-022-15518-7 |
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