Microsporidian EnP1 alters host cell H2B monoubiquitination and prevents ferroptosis facilitating microsporidia survival
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ABSTRACT:
PROVIDER: PRJNA1040798 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26841127_1.fastq.gz | Fastqsanger.gz | |||
| SRR26841127_2.fastq.gz | Fastqsanger.gz | |||
| SRR26841128_1.fastq.gz | Fastqsanger.gz | |||
| SRR26841128_2.fastq.gz | Fastqsanger.gz | |||
| SRR26841129_1.fastq.gz | Fastqsanger.gz |
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Project description:Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell's resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival.
2023-11-21 | GSE247835 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE33049: GlcNAcylation of histone H2B facilitates its monoubiquitination [Illumina Genome Analyzer data] GSE33050: GlcNAcylation of histone H2B facilitates its monoubiquitination [Affymetrix data] Refer to individual Series
2011-10-26 | E-GEOD-33051 | biostudies-arrayexpress
Project description:We report that histone GlcNAcylation of H2B S112 is a vital histone modification which facilitates histone monoubiquitination (ub). In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over entire chromosomes including transcribed gene loci, together with co-localization of H2B S112 GlcNAcylation and K120 ub. Examination of H2B S112 GlcNAc and H2B K120 ub in HeLa S3 cells
2011-10-27 | E-GEOD-33049 | biostudies-arrayexpress
Project description:We report that histone GlcNAcylation of H2B S112 is a vital histone modification which facilitates histone monoubiquitination (ub). In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over entire chromosomes including transcribed gene loci, together with co-localization of H2B S112 GlcNAcylation and K120 ub.
2011-10-27 | GSE33049 | GEO
Project description:Monoubiquitination of histone H2B on lysine 123 (H2BK123ub) is a transient histone modification considered to be essential for establishing H3K4 and H3K79 trimethylation by Set1/COMPASS and Dot1, respectively. Many of the factors such as Rad6/Bre1, the Paf1 complex, and the Bur1/Bur2 complex were identified to be required for proper histone H3K4 and H3K79 trimethylation, and were shown to function by regulating H2BK123ub levels. Here, we have identified Chd1 as a factor that is required for proper maintenance of H2B monoubiquitination levels, but not for H3K4 and H3K79 trimethylation. Loss of Chd1 results in a substantial loss of H2BK123ub levels with little to no effect on the genome-wide pattern of H3K4 and H3K79 trimethylation. Our data shows that nucleosomal occupancy is reduced in gene bodies in both CHD1 null and K123A backgrounds. We have also demonstrated that Chd1’s function in maintaining H2BK123ub levels is conserved from yeast to human. Our study provides evidence that only small levels of H2BK123ub are necessary for full levels of H3K4 and H3K79 trimethylation in vivo, and points to a role for Chd1 in positively regulating gene expression through promoting nucleosome re-assembly coupled with H2B monoubiquitination. Examination of two histone modifications in wild-type and Chd1 null yeast strains using ChIP-seq. Expression profiling in wild-type and Chd1 null yeast strains using RNA-seq.
2012-05-01 | E-GEOD-36334 | biostudies-arrayexpress
Project description:Monoubiquitination of histone H2B on lysine 123 (H2BK123ub) is a transient histone modification considered to be essential for establishing H3K4 and H3K79 trimethylation by Set1/COMPASS and Dot1, respectively. Many of the factors such as Rad6/Bre1, the Paf1 complex, and the Bur1/Bur2 complex were identified to be required for proper histone H3K4 and H3K79 trimethylation, and were shown to function by regulating H2BK123ub levels. Here, we have identified Chd1 as a factor that is required for proper maintenance of H2B monoubiquitination levels, but not for H3K4 and H3K79 trimethylation. Loss of Chd1 results in a substantial loss of H2BK123ub levels with little to no effect on the genome-wide pattern of H3K4 and H3K79 trimethylation. Our data shows that nucleosomal occupancy is reduced in gene bodies in both CHD1 null and K123A backgrounds. We have also demonstrated that Chd1’s function in maintaining H2BK123ub levels is conserved from yeast to human. Our study provides evidence that only small levels of H2BK123ub are necessary for full levels of H3K4 and H3K79 trimethylation in vivo, and points to a role for Chd1 in positively regulating gene expression through promoting nucleosome re-assembly coupled with H2B monoubiquitination.
2012-05-02 | GSE36334 | GEO
Project description:Extensive changes in post-translational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs), various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSC. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSC cells and plays a central role in controlling stem cell differentiation.
2013-01-03 | GSE38173 | GEO
Project description:In eukaryotes, chromatin-based mechanisms superimpose with DNA sequence information to determine the transcriptional output of the genome. Therefore, evaluating the role of chromatin modifications in the regulation of gene expression is key to understand the contribution of chromatin state variations to development. Recent studies identified several transcriptional coactivators that contribute to selectively regulate cellular pathways by coordinating histone H2B monoubiquitination (H2Bub) with other histone modifications. Although H2Bub is present on a large number of genes, loss of H2B monoubiquitination activity was shown to affect RNA steady levels for a small subset of genes and therefore its influence on gene expression is not well understood. In this study we assessed the impact of H2Bub on dynamic expression changes during a rapid developmental tranistion that initiates only when exposing plants to light. This revealed that H2Bub deposition is highly dynamic in a genomic context. Furthermore, plants lacking histone H2B monoubiquitination activity were impaired for rapid changes of RNA levels for a large repertoire of genes, indicating that H2Bub is important for attaining appropriate expression levels /in fine/. Finally, the detection power of the genomic approach has allowed us to define a set of genes impacted by H2Bub dynamics for rapid changes in RNA levels. The purpose of this study was to integrate the genome-wide distribution of H2Bub chromatin mark together with transcriptome profiles of wild-type and /hub1 /mutant plants (accession GSE21922) at three time points during early photomorphogenesis H2Bub epigenome in 5-day-old dark-grown seedlings, H2Bub epigenome in 5-day-old dark-grown seedlings +1h light, and H2Bub epigenome in 5-day-old dark-grown seedlings +6h light 2 biological replicates for each time point in dye-swap - ChIP-chip
2013-03-13 | E-GEOD-36515 | biostudies-arrayexpress
Project description:Extensive changes in post-translational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs), various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of differentiation markers and transcriptional reprogramming of hMSC. This function is dependent upon CDK9 and the WAC adaptor protein, which are required for H2B monoubiquitination. Finally, we show that RNF40 is required for the resolution of the H3K4me3/H3K27me3 bivalent poised state on lineage-specific genes during the transition from an inactive to active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSC cells and plays a central role in controlling stem cell differentiation. This set contains 29 microarray samples and includes the following 5 conditions: undifferentiated hMSCs, 2 day osteoblast differentiation, 5 day osteoblast differentiation, 2 day adipocyte differentiation, and 5 day adipocyte differentiation. 3 siRNA control samples and 3 RNF40 knockdown samples for each condition (except two control siRNA samples for 2 days osteoblast differentiation).
2013-01-03 | E-GEOD-38173 | biostudies-arrayexpress
Project description:In eukaryotes, chromatin-based mechanisms superimpose with DNA sequence information to determine the transcriptional output of the genome. Therefore, evaluating the role of chromatin modifications in the regulation of gene expression is key to understand the contribution of chromatin state variations to development. Recent studies identified several transcriptional coactivators that contribute to selectively regulate cellular pathways by coordinating histone H2B monoubiquitination (H2Bub) with other histone modifications. Although H2Bub is present on a large number of genes, loss of H2B monoubiquitination activity was shown to affect RNA steady levels for a small subset of genes and therefore its influence on gene expression is not well understood. In this study we assessed the impact of H2Bub on dynamic expression changes during a rapid developmental tranistion that initiates only when exposing plants to light. This revealed that H2Bub deposition is highly dynamic in a genomic context. Furthermore, plants lacking histone H2B monoubiquitination activity were impaired for rapid changes of RNA levels for a large repertoire of genes, indicating that H2Bub is important for attaining appropriate expression levels /in fine/. Finally, the detection power of the genomic approach has allowed us to define a set of genes impacted by H2Bub dynamics for rapid changes in RNA levels. The purpose of this study was to integrate the genome-wide distribution of H2Bub chromatin mark together with transcriptome profiles of wild-type and /hub1 /mutant plants (accession GSE21922) at three time points during early photomorphogenesis
2013-03-13 | GSE36515 | GEO