Decreases in monoubiquitination of histone H2B is a critical regulator of age-related memory decline
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ABSTRACT:
PROVIDER: PRJNA1198963 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31736522_1.fastq.gz | Fastqsanger.gz | |||
| SRR31736522_2.fastq.gz | Fastqsanger.gz | |||
| SRR31736523_1.fastq.gz | Fastqsanger.gz | |||
| SRR31736523_2.fastq.gz | Fastqsanger.gz | |||
| SRR31736524_1.fastq.gz | Fastqsanger.gz |
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Project description:We report a critical role of decreased monoubiquitination of H2B (H2Bubi) in age-related memory decline. We found that contextual fear conditioning in aged rats led to modest transcriptional changes in the hippocampus, which was correlated with impaired memory. Conversely, CRISPR-dCas9-mediated increases in the H2Bubi ligase, Rnf20, in the hippocampus improved memory in aged rats and resulted in a more robust transcriptome. Surprisingly, 18 genes upregulated with learning in the control group was also found in the rnf20 upregulation condition, though the later included more than 20 additional upregulated and 10 downregulated genes. These data suggest that upregulating H2Bubi in the aged hipocampus may improve memory by controlling transcriptional changes in a subset of memory critical genes
2025-05-22 | GSE284407 | 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:Ubiquitination has crucial roles in many cellular processes and dysregulation of ubiquitin machinery enzymes can result in various forms of pathogenesis. Cells only have a limited set of E2 ubiquitin-conjugating enzymes to support the ubiquitination of many cellular targets. As individual E2 enzymes have many different substrates and interactions between E2 enzymes and their substrates can be transient, it is challenging to define all in vivo substrates of an individual E2 and the cellular processes it affects. Particularly challenging in this respect is UBE2D3, a very promiscuous E2 enzyme that affects a broad range of processes. Here, we set out to identify in vivo targets of UBE2D3 by using SILAC-based quantitative ubiquitin diGly proteomics to study global proteome and ubiquitinome changes associated with UBE2D3 depletion. UBE2D3 depletion changed the global proteome, with proteins from metabolic pathways, in particular retinol metabolism, being the most affected. However, the impact of UBE2D3 depletion on the ubiquitinome was much more prominent and, interestingly, identified pathways related to mRNA translation as top pathways being affected. Indeed, we find that ubiquitination of the ribosomal proteins RPS10 and RPS20, critical for ribosome-associated protein quality control (RQC), is dependent on UBE2D3. Moreover, we find that UBE2D3 limits monoubiquitination of histone H2B at lysine 120, mediated by the E3 ligase RNF20. This identifies UBE2D3 as a potential regulator of the diverse and critical cellular processes that are controlled by H2B monoubiquitination. Collectively, our findings show that depletion of an E2 ubiquitin-conjugating enzyme in combination with quantitative diGly-based ubiquitinome profiling is a powerful tool to identify new in vivo E2 substrates, as we have done here for UBE2D3. Together with our identification of RQC factors and H2B as novel in vivo targets of UBE2D3, our work provides an important resource for further studies on the in vivo functions of UBE2D3.
2023-04-12 | PXD026054 | Pride
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