Genome-wide H2B monoubiquitination regulates gene expression by coordinating H3K4me3 and H3K27me3
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ABSTRACT:
PROVIDER: PRJNA293453 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2176230.fastq.gz | Fastqsanger.gz | |||
| SRR2176240.fastq.gz | Fastqsanger.gz | |||
| SRR2176250.fastq.gz | Fastqsanger.gz | |||
| SRR2176260.fastq.gz | Fastqsanger.gz | |||
| SRR2176231.fastq.gz | Fastqsanger.gz |
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Project description:Gene body-associated monoubiquitination of H2B (H2Bub1) coupled with promoter-associated active histone modifications such as trimethylation H3 on lysine 4 (H3K4me3) and acetylation H3 on lysine 27 (H3K27ac) facilitate gene transcription. However, surprisingly, only a subset of genes is altered in their expression following knockdown of H2B ubiquitin-protein ligases RNF20 or RNF40 in human cells. In order to obtain a more complete genome- and transcriptome-wide understanding of the role of H2Bub1 in gene transcription, we generated tamoxifen-inducible Rnf40 knockout mouse embryonic fibroblasts (MEFs). Mapping of H2Bub1, H3K4me3, H3K27me3, and H3K27ac occupancy identified an “ascending” gene cluster including bivalent genes, which is occupied by low to moderate amounts of H2Bub1 and exhibits high variability in transcription. We provide evidence that the variation in expression is highly associated with the variations in H3K4me3, H3K27me3, and H3K27ac occupancy. Moreover, these variably marked “ascent” genes are selectively regulated in Rnf40-deficient MEFs. Consistent with previous studies, the effect of Rnf40 loss on the expression of genes within this cluster is also variable with some genes demonstrating increased while others decreased mRNA levels following Rnf40 deletion. Importantly, we identified the Ezh2 gene as an Rnf40/H2Bub1 target whose expression significantly decreased in Rnf40-deficient MEFs. Notably, we show that genes upregulated following Rnf40 deletion are enriched for H3K27me3, which is decreased following Rnf40 deletion, and these effects can be mimicked by treating with a small molecule EZH2 inhibitor. On the other hand, consistent with findings in many eukaryotic systems, genes whose expression decreases following Rnf40 deletion show an enrichment of H3K4me3 and decreased levels following deletion. Together, we provide mechanistic information by which Rnf40, presumably via H2Bub1, modulates gene expression via coordination of the active and repressive marks H3K4me3 and H3K27me3.
2017-01-05 | GSE72238 | GEO
Project description:Gene body-associated monoubiquitination of H2B (H2Bub1) coupled with promoter-associated active histone modifications such as trimethylation H3 on lysine 4 (H3K4me3) and acetylation H3 on lysine 27 (H3K27ac) facilitate gene transcription. However, surprisingly, only a subset of genes is altered in their expression following knockdown of H2B ubiquitin-protein ligases RNF20 or RNF40 in human cells. In order to obtain a more complete genome- and transcriptome-wide understanding of the role of H2Bub1 in gene transcription, we generated tamoxifen-inducible Rnf40 knockout mouse embryonic fibroblasts (MEFs). Mapping of H2Bub1, H3K4me3, H3K27me3, and H3K27ac occupancy identified an “ascending” gene cluster including bivalent genes, which is occupied by low to moderate amounts of H2Bub1 and exhibits high variability in transcription. We provide evidence that the variation in expression is highly associated with the variations in H3K4me3, H3K27me3, and H3K27ac occupancy. Moreover, these variably marked “ascent” genes are selectively regulated in Rnf40-deficient MEFs. Consistent with previous studies, the effect of Rnf40 loss on the expression of genes within this cluster is also variable with some genes demonstrating increased while others decreased mRNA levels following Rnf40 deletion. Importantly, we identified the Ezh2 gene as an Rnf40/H2Bub1 target whose expression significantly decreased in Rnf40-deficient MEFs. Notably, we show that genes upregulated following Rnf40 deletion are enriched for H3K27me3, which is decreased following Rnf40 deletion, and these effects can be mimicked by treating with a small molecule EZH2 inhibitor. On the other hand, consistent with findings in many eukaryotic systems, genes whose expression decreases following Rnf40 deletion show an enrichment of H3K4me3 and decreased levels following deletion. Together, we provide mechanistic information by which Rnf40, presumably via H2Bub1, modulates gene expression via coordination of the active and repressive marks H3K4me3 and H3K27me3.
2017-01-05 | GSE72237 | 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: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: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: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: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: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: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
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-01-05 | GSE72239 | GEO