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Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii. [RNA-seq]

ABSTRACT: Toxoplasma gondii is a unicellular eukaryote belonging to the Apicomplexa phylum. It is an obligate intracellular parasite of critical importance to primarily infected pregnant women and immunosuppressed patient. ApiAP2 are a family of conserved transcription factors (TF) that play an important role in regulating gene expression in apicomplexan parasites. Previous studies had revealed the ability of one of these TFs, TgAP2XI-5, to bind to transcriptionally active promoters of genes expressed during the S/M phase such as rhoptry and micronemes genes. However, expression of TgAP2XI-5 is constitutive during the tachyzoite cell cycle. To better understand how its function is regulated, we identified proteins interacting with TgAP2XI-5 including a cell cycle regulated ApiAP2 TFs, TgAP2X-5. The purpose of the study is to determine the impact of the absence of a TF (TgAP2X-5) on the wide expression profile of a Toxoplasma gondii strain.

ORGANISM(S): Toxoplasma gondii

PROVIDER: GSE106864 | GEO | 2018/05/30

REPOSITORIES: GEO

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Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii. [ChIP-chip]

Project description:Toxoplasma gondii is a unicellular eukaryote belonging to the Apicomplexa phylum. It is an obligate intracellular parasite of critical importance to primarily infected pregnant women and immunosuppressed patient. ApiAP2 are a family of conserved transcription factors (TF) that play an important role in regulating gene expression in apicomplexan parasites. Previous studies had revealed the ability of one of these TFs, TgAP2XI-5, to bind to transcriptionally active promoters of genes expressed during the S/M phase such as rhoptry and micronemes genes. However, expression of TgAP2XI-5 is constitutive during the tachyzoite cell cycle. To better understand how its function is regulated, we identified proteins interacting with TgAP2XI-5 including a cell cycle regulated ApiAP2 TFs, TgAP2X-5. The purpose of the study is to determine the impact of the absence of TgAP2X-5 on the binding of TgAP2XI-5 on its targets. Chromatin immunoprecipitation (ChIP) of TgAP2XI-5 together with chromatin in absence of TgAP2X-5 profiling by ChIP-on-chip analysis demonstrated that TgAP2X-5 co-acts with TgAP2XI-5 for its binding to DNA of certain promoter targets.

2018-05-30 | GSE109086 | GEO

Toxoplasma gondii transcription factor AP2XII-8 is a key regulator for the G1 phase progression and parasite division

Project description:The apicomplexan parasite Toxoplasma gondii can infect humans and almost all warm-blooded animals worldwide, poses significant threat to the public health and of veterinary importance. The acute infection was characterized by fast replication of tachyzoites inside the host cells. During this fast amplification process, the gene expression is highly regulated by series of regulator networks. The G1 phase is usually conserved across species and responsible for the preparation of materials for the next replication cell cycle, but seldom regulators were identified in this stage. Here, we functionally characterized the C/G1 phase expressed ApiAP2 transcription factor TgAP2XII-8 in T. gondii tachyzoite. Conditionally knockdown of TgAP2XII-8 leads to significant growth defects and asexual division disorder. Additionally, the parasite cell cycle progression was also disrupted after TgAP2XII-8 depletion, which is characterized by G1 phase arrest. RNA-seq and CUT&Tag experiments revealed that TgAP2XII-8 played as an activator for the ribosomal proteins expressed in G1 phase. Moreover, TgAP2XII-8 bind to a specific DNA motif ([T/C]GCATGCA), which is abundant and conserved in the intergenic region of several other apicomplexans, which may suggest a broad and conserved role for this ApiAP2 in the Phylum of Apicomplexa. These data provide important knowledge for the understanding of transcriptional regulation of parasite cell cycle in T. gondii.

2024-08-25 | GSE275112 | GEO

Dual RNA-seq analysis of pig alveolar macrophage infected with china-isolated TgHB1 compared to TgRH and TgMe49 toxoplasma gondii standard strain

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.

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An apicomplexan bromodomain protein, TgBDP1 associates with diverse epigenetic factors to regulate essential transcriptional processes in Toxoplasma gondii

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.

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Identification of RON13 binding with with RON4 substrate

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2021-05-10 | PXD023791 | Pride

A single master regulator controls asexual cell cycle division patterns in Toxoplasma gondii [ChIP-Seq]

Project description:ApiAP2 are a family of conserved transcription factors (TF) that play an important role in regulating gene expression in apicomplexan parasites. ApiAP2 proteins that may control the cell cycle dependent expression program are to be discovered. To better understand how these cell-cycle dependent gene expression profiles are established, we identified ApiAP2 proteins showing a cell cycle dependent expression. Using the Auxin-degradation system, we produced several inducible knock-down (iKD) mutant for these ApiAP2 proteins. Among them, a cell-cycle regulated ApiAP2 is expressed during the late S-phase of the tachyzoite cell-cycle. The iKD mutant parasites for this gene are unable to proliferate. In presence of Auxin, the mutant parasites do not produce daughter cells and are arrested in the early phase of budding. This indicates that this TF may specifically regulate the early steps of the daughter cell formation. Using RNA-Seq, we demonstrate that the level of expression of number of transcripts is affected by the knock-down of this potential TF.

2020-10-29 | GSE150405 | GEO

A single master regulator controls asexual cell cycle division patterns in Toxoplasma gondii [RNA-Seq]

2020-10-29 | GSE150334 | GEO

An apicomplexan bromodomain, TgBDP1 associates with diverse epigenetic factors to regulate essential transcriptional processes in Toxoplasma gondii.

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

Expression QTL mapping of Toxoplasma gondii genes

Project description:This SuperSeries is composed of the following subset Series: GSE11437: Expression QTL mapping of Toxoplasma gondii genes, Bradyzoite array GSE11514: Expression QTL mapping of Toxoplasma gondii genes, Tachyzoite array Keywords: SuperSeries Refer to individual Series

2008-05-22 | E-GEOD-11515 | biostudies-arrayexpress

Coordinated Progression Through Two Subtranscriptomes Underlies the Tachyzoite Cycle of Toxoplasma gondii

Project description:We describe the cell cycle transcriptome of the Toxoplasma gondii that has emerged as a major genetic model for the study of Apicomplexa parasites. Two distinct transcriptional waves accompany the relatively simple binary replication of tachyzoite stage (endodyogeny) functionally separating conserved gene expression in the eukaryotic G1 phase from the lineage-specific expression that predominates in the parasite S phase and mitotic periods. This division of transcriptional focus closely mirrors the intimate relationship that has evolved between mitosis and building of the daughter parasites and invasion organelles. Promoter mechanisms appear to orchestrate the induction of gene expression in dividing tachyzoites with up to two dozen cell cycle AP2 factors likely acting within a transcriptional regulatory network to coordinate the parasite cell cycle transcriptome. To characterize the cell cycle transcriptome of Toxoplasma tachyzoites, we expanded a thymidine-synchrony model to isolate sufficient RNA for microarray expression studies. The ToxoGeneChip microarray (http://ancillary.toxodb.org/docs/Array-Tutorial.html) was used to measure mRNA expression in 13 duplicate samples (R0 to R12) covering 12 hours post-synchronization and nearly two tachyzoite replication cycles.

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