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Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion
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 d...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325746/ https://www.ncbi.nlm.nih.gov/pubmed/35882887 http://dx.doi.org/10.1038/s41598-022-15518-7 |
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author | Tajeri, Shahin Momeux, Laurence Saintpierre, Benjamin Mfarrej, Sara Chapple, Alexander Mourier, Tobias Shiels, Brian Ariey, Frédéric Pain, Arnab Langsley, Gordon |
author_facet | Tajeri, Shahin Momeux, Laurence Saintpierre, Benjamin Mfarrej, Sara Chapple, Alexander Mourier, Tobias Shiels, Brian Ariey, Frédéric Pain, Arnab Langsley, Gordon |
author_sort | Tajeri, Shahin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9325746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93257462022-07-28 Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion Tajeri, Shahin Momeux, Laurence Saintpierre, Benjamin Mfarrej, Sara Chapple, Alexander Mourier, Tobias Shiels, Brian Ariey, Frédéric Pain, Arnab Langsley, Gordon Sci Rep Article 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. Nature Publishing Group UK 2022-07-26 /pmc/articles/PMC9325746/ /pubmed/35882887 http://dx.doi.org/10.1038/s41598-022-15518-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tajeri, Shahin Momeux, Laurence Saintpierre, Benjamin Mfarrej, Sara Chapple, Alexander Mourier, Tobias Shiels, Brian Ariey, Frédéric Pain, Arnab Langsley, Gordon Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion |
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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325746/ https://www.ncbi.nlm.nih.gov/pubmed/35882887 http://dx.doi.org/10.1038/s41598-022-15518-7 |
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