An apicomplexan bromodomain protein, TgBDP1 associates with diverse epigenetic factors to regulate essential transcriptional processes in Toxoplasma gondii
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA951737 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24055250_1.fastq.gz | Fastqsanger.gz | |||
| SRR24055250_2.fastq.gz | Fastqsanger.gz | |||
| SRR24055251_1.fastq.gz | Fastqsanger.gz | |||
| SRR24055251_2.fastq.gz | Fastqsanger.gz | |||
| SRR24055252_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:The protozoan pathogen Toxoplasma gondii relies on tight regulation of gene expression to invade and establish infection in its host. The divergent gene regulatory mechanisms of Toxoplasma and related apicomplexan pathogens rely heavily on regulators of chromatin structure and histone modifications. The important contribution of histone acetylation for Toxoplasma in both acute and chronic infection has been demonstrated, where histone acetylation increases at active gene loci. However, the direct consequences of specific histone acetylation marks and the chromatin pathway that influences transcriptional regulation in response to the modification is unclear. As a reader of lysine acetylation, the bromodomain serves as a mediator between the acetylated histone and transcriptional regulators. Here we show that the bromodomain protein TgBDP1 which is conserved amongst Apicomplexa and within the Alveolata superphylum, is essential for Toxoplasma asexual proliferation. Using CUT&TAG we demonstrate that TgBDP1 is recruited to transcriptional start sites of a large proportion of parasite genes. Transcriptional profiling during TgBDP1 knockdown revealed that loss of TgBDP1 leads to major dysregulation of gene expression, implying multiple roles for TgBDP1 in both gene activation and repression. This is supported by interactome analysis of TgBDP1 demonstrating that TgBDP1 forms a core complex with two other bromodomain proteins and an ApiAP2 factor. This core complex appears to interact with other epigenetic factors such as nucleosome remodelling complexes. We conclude that TgBDP1 interacts with diverse epigenetic regulators to exert opposing influences on gene expression in the Toxoplasma tachyzoite.
2023-05-31 | GSE228853 | GEO
Project description:The protozoan pathogen Toxoplasma gondii relies on tight regulation of gene expression to invade and establish infection in its host. The divergent gene regulatory mechanisms of Toxoplasma and related apicomplexan pathogens rely heavily on regulators of chromatin structure and histone modifications. The important contribution of histone acetylation for Toxoplasma in both acute and chronic infection has been demonstrated, where histone acetylation increases at active gene loci. However, the direct consequences of specific histone acetylation marks and the signaling pathway that influences transcriptional regulation in response to the modification is unclear. As a reader of lysine acetylation, the bromodomain serves as a mediator between the acetylated histone and transcriptional regulators. Here we show that the bromodomain protein TgBDP1 which is conserved amongst Apicomplexa and within the Alveolata superphylum, is essential for Toxoplasma asexual proliferation. Using CUT&TAG we demonstrate that TgBDP1 is recruited to transcriptional start sites of a large proportion of parasite genes. Transcriptional profiling during TgBDP1 knockdown revealed that loss of TgBDP1 leads to major dysregulation of gene expression, implying multiple roles for TgBDP1 in both gene activation and repression. This is supported by interactome analysis of TgBDP1 demonstrating that TgBDP1 forms a core complex with two other bromodomain proteins and an ApiAP2 factor. This core complex appears to interact with other epigenetic factors such as nucleosome remodelling complexes. We conclude that TgBDP1 interacts with diverse epigenetic regulators to exert opposing influences on gene expression in the Toxoplasma tachyzoite.
2023-06-01 | PXD038848 | Pride
Project description:The protozoan pathogen Toxoplasma gondii relies on tight regulation of gene expression to invade and establish infection in its host. The divergent gene regulatory mechanisms of Toxoplasma and related apicomplexan pathogens rely heavily on regulators of chromatin structure and histone modifications. The important contribution of histone acetylation for Toxoplasma in both acute and chronic infection has been demonstrated, where histone acetylation increases at active gene loci. However, the direct consequences of specific histone acetylation marks and the chromatin pathway that influences transcriptional regulation in response to the modification are unclear. As a reader of lysine acetylation, the bromodomain serves as a mediator between the acetylated histone and transcriptional regulators. Here we show that the bromodomain protein, TgBDP1, which is conserved among Apicomplexa and within the Alveolata superphylum, is essential for Toxoplasma asexual proliferation. Using cleavage under targets and tagmentation, we demonstrate that TgBDP1 is recruited to transcriptional start sites of a large proportion of parasite genes. Transcriptional profiling during TgBDP1 knockdown revealed that loss of TgBDP1 leads to major dysregulation of gene expression, implying multiple roles for TgBDP1 in both gene activation and repression. This is supported by interactome analysis of TgBDP1 demonstrating that TgBDP1 forms a core complex with two other bromodomain proteins and an ApiAP2 factor. This core complex appears to interact with other epigenetic factors such as nucleosome remodeling complexes. We conclude that TgBDP1 interacts with diverse epigenetic regulators to exert opposing influences on gene expression in the Toxoplasma tachyzoite. IMPORTANCE Histone acetylation is critical for proper regulation of gene expression in the single-celled eukaryotic pathogen Toxoplasma gondii. Bromodomain proteins are "readers" of histone acetylation and may link the modified chromatin to transcription factors. Here, we show that the bromodomain protein TgBDP1 is essential for parasite survival and that loss of TgBDP1 results in global dysregulation of gene expression. TgBDP1 is recruited to the promoter region of a large proportion of parasite genes, forms a core complex with two other bromodomain proteins, and interacts with different transcriptional regulatory complexes. We conclude that TgBDP1 is a key factor for sensing specific histone modifications to influence multiple facets of transcriptional regulation in Toxoplasma gondii.
| S-EPMC10470533 | biostudies-literature
Project description:Toxoplasma gondii is an apicomplexan parasite infecting human and animals, causing huge health concerns and economic losses. Calcium ion, a critical second messenger in cells, can regulate related vital activities, particularly in parasite invasion and escape processes. Calmodulin (CaM) is a short, highly conserved Ca2+ binding protein found in all eukaryotic cells, including apicomplexan parasites. After binding to Ca2+, CaM can be activated to interact with a variety of proteins (such as enzymes). Since direct destruction of CaM is impossible, few studies have been conducted on the function of CaM in T. gondii. We generated the CaM indirect knockout strain (iCaM) using a tetracycline-off system with CaM promoter sequence in T. gondii TATI strain, and compared the transcriptomes of tachyzoites with and without Calmodulin.
2022-04-14 | GSE198001 | GEO
Project description:Tartrolon E is a pan anti-apicomplexan compound derived from a symbiotic bacteria of shipworms. The mechanism of action of the compound is unknown, and attempts to select parasite mutants resistant to the compound has been unsuccessful. In this study, RNAseq was performed on human foreskin fibroblast cells (HFF) infected with Toxoplasma gondii RH strain and treated with Tartrolon E to identify genes targeted by the compound.
2019-11-12 | GSE140197 | GEO
Project description:Toxoplasma gondii and Cryptosporidium species are apicomplexan parasites of significant medical and veterinary importance. Although current therapeutic options for toxoplasmosis and cryptosporidiosis demonstrate notable efficacy, their clinical efficacy is often limited by suboptimal efficacy and frequent adverse effects. Moreover, therapeutic alternatives remain limited or nonexistent, particularly for cryptosporidiosis, for which nitazoxanide is currently the only approved medication to treat diarrhea in adults and children older than 1 year of age. To identify alternative therapeutic options for addressing these health challenges, we performe a phenotypic screening of an FDA-approved drug repurposing library against Toxoplasma. This screening identifies LY2090314 as a potent inhibitor of T. gondii and Cryptosporidium growth in mammalian cells. Through a target deconvolution strategy combining forward genetics, transcriptome sequencing, and computational mutation analysis, we elucidate the parasiticidal mechanism of LY2090314 and demonstrate that TgGSK3 kinase is its primary molecular target. We also report the first X-ray crystal structure of LY2090314 bound to TgGSK3, resolved at 2.1 Å, which reveals an interaction mode characteristic of type I ATP-competitive inhibitors. Furthermore, interactome analysis uncovers functional connections between TgGSK3 and key cytoskeletal and signaling regulators, providing insights into compound’s effects. Collectively, these findings validate TgGSK3 as a promising therapeutic target for toxoplasmosis and offer mechanistic insights into apicomplexan GSK3 biology.
2025-01-20 | GSE286338 | GEO
Project description:Toxoplasma gondii is an apicomplexan parasite infecting human and animals, causing huge health concerns and economic losses. However, it is unclear about the exact mechanism of T.gondii tachyzoite infected macrophage and macrophage resisted T.gondii, especially for local isolates such as TgHB1 isolated in China. Our study focused on the transcriptional difference of pig alveolar macrophages (3D4/21) infected with china isolated TgHB1 compared to TgRH and TgME49 toxoplasma gondii standard strains.
2020-09-12 | GSE153330 | GEO
Project description:Toxoplasma gondii is an apicomplexan parasite that approximately infects one third of the human population worldwide. When sporulated oocysts that are shed in the faeces of infected felids are accidentally ingested through contaminated food or water, sporozoites can infect the intestine of the intermediate host. Upon this infection, the fast replicating tachyzoites then disseminate overall the body and can cross the blood-brain, blood-retina or the blood-placenta barrier. Eventually, immune pressure will lead to differentiation into the slow replicating bradyzoites that are contained within tissue cysts for life. Despite the importance of sporulation for transmission, the process is not yet understood. We therefore exploited Illumina Next-Generation RNA-Sequencing to analyse the transcriptome of oocysts in the process of sporulation and compared it to unsporulated and sporulated oocysts. We thus identified genes that are highly specific to the sporulation process and that may be involved in the formation of sporozoites.
2022-06-20 | GSE206344 | GEO