Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA
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ABSTRACT:
PROVIDER: PRJNA643273 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12121817.fastq.gz | Fastqsanger.gz | |||
| SRR12121818.fastq.gz | Fastqsanger.gz | |||
| SRR12121819.fastq.gz | Fastqsanger.gz | |||
| SRR12121820.fastq.gz | Fastqsanger.gz | |||
| SRR12121821.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The deubiquitinating module (DUBm) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and ATXN7, ATXN7L3 and ENY2 adaptor proteins, which are all needed for the full activity of USP22 enzyme. In addition, ATXN7L3 is critical for directing the DUB module substrate specificity towards H2Bub1. We reported that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, while in contrast H2Bub1 levels were strongly increased in Atxn7l3 null mutants and derived cellular systems. Interestingly, the strong H2Bub1 increases observed in the Atxn7l3-/- mouse embryonic stem cells, or Atxn7l3-/- mouse embryonic fibroblasts, do not correlate with the modest genome-wide Pol II occupancy changes observed in the two knock-out cellular systems. Thus, histone H2Bub1 deubiquitylation does not directly regulate global RNA polymerase II transcription.
2021-02-16 | GSE153578 | GEO
Project description:The deubiquitinating module (DUBm) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and ATXN7, ATXN7L3 and ENY2 adaptor proteins, which are all needed for the full activity of USP22 enzyme. In addition, ATXN7L3 is critical for directing the DUB module substrate specificity towards H2Bub1. We reported that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, while in contrast H2Bub1 levels were strongly increased in Atxn7l3 null mutants and derived cellular systems. Interestingly, the strong H2Bub1 increases observed in the Atxn7l3-/- mouse embryonic stem cells, or Atxn7l3-/- mouse embryonic fibroblasts, do not correlate with the modest genome-wide Pol II occupancy changes observed in the two knock-out cellular systems. Thus, histone H2Bub1 deubiquitylation does not directly regulate global RNA polymerase II transcription.
2021-02-16 | GSE153584 | GEO
Project description:Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA [ChIP-Seq]
| PRJNA643279 | ENA
Project description:Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA [RNA-Seq]
| PRJNA643265 | ENA
Project description:Co-activator complexes dynamically deposit post-translational modifications (PTMs) on histones, or remove them, to regulate chromatin accessibility and/or to create/erase docking surfaces for proteins that recognize histone PTMs. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved multisubunit co-activator complex with modular organization. The deubiquitylation module (DUB) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and three adaptor proteins, ATXN7, ATXN7L3 and ENY2, which are all needed for the full activity of the USP22 enzyme to remove monoubiquitin (ub1) from histone H2B. Two additional USP22-related ubiquitin hydrolases (called USP27X or USP51) have been described to form alternative DUBs with ATXN7L3 and ENY2, which can also deubiquitylate H2Bub1. Here we report that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process, as Atxn7l3-/- embryos show developmental delay already at embryonic day (E) 7.5, while Usp22-/- embryos are normal at this stage, but die at E14.5. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, in contrast H2Bub1 levels were strongly increased in Atxn7l3 null embryos and derived cell lines. Our transcriptomic analyses carried out from wild type and Atxn7l3-/- mouse embryonic stem cells (mESCs), or primary mouse embryonic fibroblasts (MEFs) suggest that the ATXN7L3-related DUB activity regulates only a subset of genes in both cell types. However, the gene sets and the extent of their deregulation were different in mESCs and MEFs. Interestingly, the strong increase of H2Bub1 levels observed in the Atxn7l3-/- mESCs, or Atxn7l3-/- MEFs, does not correlate with the modest changes in RNA Polymerase II (Pol II) occupancy and lack of changes in Pol II elongation observed in the two Atxn7l3-/- cellular systems. These observations together indicate that deubiquitylation of histone H2Bub1 does not directly regulate global Pol II transcription elongation.
| S-EPMC8329007 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-16 | GSE153587 | GEO
Project description:Histone H2B mono-ubiquitylation (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. How Cdk9 activity and H2Bub1 cooperate to regulate the expression of individual genes remains unclear. Here we show Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of distinct gene subsets; ablation of both pathways derepresses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both are enriched in coding regions, and H2Bub1 levels are directly proportional to those of phospho-Spt5. Cdk9-dependence of antisense suppression correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Combined reduction of Cdk9 activity and loss of H2Bub1 prevent recruitment of the histone deacetylase Clr6-CII to transcribed genes, and lead to decreased histone occupancy and increased histone acetylation within gene coding regions. These results uncover new pathways linking regulators of RNAPII transcription elongation to suppression of aberrant antisense transcription, and demonstrate novel interactions between co-transcriptional histone modification pathways.
2020-05-21 | GSE115682 | GEO
Project description:Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved patterns of histone modification within transcribed regions, but it remains uncertain how these modifications influence, or are influenced by, properties of the elongation complex. Here we establish an intimate link between Cdk9, the kinase component of positive transcription elongation factor b (P-TEFb), and mono-ubiquitylation of histone H2B (H2Bub1), in the fission yeast Schizosaccharomyces pombe. Mutations that impair Cdk9 function reduce H2Bub1 levels in vivo. Conversely, mutations that prevent H2Bub1 decrease phosphorylation of elongation factor subunit Spt5, a sensitive and specific indicator of Cdk9 activity. Chromatin immunoprecipitation (ChIP) analysis suggests this is due to impaired Cdk9 recruitment to H2Bub1-deficient chromatin. P-TEFb and H2Bub1 pathways also interact genetically: mutation of the histone H2B ubiquitin-acceptor residue decreases the requirement for Cdk9 activity in vivo, and multiple cdk9 mutations suppress morphological defects of H2Bub1-deficient strains. Moreover, H2Bub1 loss causes redistribution of transcribing RNAPII on chromatin that is corrected by a hypomorphic cdk9 mutation. Therefore, whereas mutual dependence of Spt5 phosphorylation and H2Bub1 suggests positive feedback between P-TEFb and the ubiquitylation machinery, mutual suppression by cdk9 and H2Bub1-pathway mutations indicates an antagonistic relationship, whereby the activities must be balanced to properly regulate elongation. In order to study the genome-wide localization of H2Bub1 in Schizosaccharomyces pombe, H2Bub1, H2B-Flag as well as RNAPII (along with associated DNA sequences) were immunoprecipitated using repectively anti-H2Bub1, anti-Flag and anti-8WG16 antibodies. The ChIPs were performed in duplicate from WT cells as well as in the H2B-K119R mutant. The extracted DNA was hybridized to a DNA microarray containing an average of 4 probes per kilobase across the whole yeast genome. The combined datasets are available in the supplemental files of the related publication.
2012-12-01 | E-GEOD-31070 | biostudies-arrayexpress
Project description:De novo variants affecting monoubiquitination of histone H2B (H2Bub1) are enriched in human congenital heart disease. H2Bub1 is required in stem cell differentiation, cilia function, post-natal cardiomyocyte maturation, and transcriptional elongation. However, how H2Bub1 affects cardiogenesis is unknown. We show that the H2Bub1-deposition complex (RNF20-RNF40-UBE2B) is required for mouse cardiogenesis and for differentiation of human iPSCs into cardiomyocytes. Mice with cardiac-specific Rnf20 deletion are embryonic lethal and have abnormal myocardium. We then analyzed H2Bub1 marks during differentiation of human iPSCs into cardiomyocytes. H2Bub1 is erased from most genes at transition from cardiac mesoderm to cardiac progenitor cells, but is preserved on a subset of long cardiac-specific genes. When H2Bub1 is reduced in iPSC-cardiomyocytes, long cardiac-specific genes have fewer full-length transcripts. This correlates with H2Bub1 accumulation near the center of these genes. H2Bub1 accumulation near the center of tissue-specific genes was also observed in embryonic fibroblasts and fetal osteoblasts. In summary, we show that normal H2Bub1 distribution is required for cardiogenesis and cardiomyocyte differentiation, and point to H2Bub1 regulating tissue-specific gene expression by increasing the amount of full-length transcripts.
2023-10-31 | GSE246410 | GEO
Project description:De novo variants affecting monoubiquitination of histone H2B (H2Bub1) are enriched in human congenital heart disease. H2Bub1 is required in stem cell differentiation, cilia function, post-natal cardiomyocyte maturation, and transcriptional elongation. However, how H2Bub1 affects cardiogenesis is unknown. We show that the H2Bub1-deposition complex (RNF20-RNF40-UBE2B) is required for mouse cardiogenesis and for differentiation of human iPSCs into cardiomyocytes. Mice with cardiac-specific Rnf20 deletion are embryonic lethal and have abnormal myocardium. We then analyzed H2Bub1 marks during differentiation of human iPSCs into cardiomyocytes. H2Bub1 is erased from most genes at transition from cardiac mesoderm to cardiac progenitor cells, but is preserved on a subset of long cardiac-specific genes. When H2Bub1 is reduced in iPSC-cardiomyocytes, long cardiac-specific genes have fewer full-length transcripts. This correlates with H2Bub1 accumulation near the center of these genes. H2Bub1 accumulation near the center of tissue-specific genes was also observed in embryonic fibroblasts and fetal osteoblasts. In summary, we show that normal H2Bub1 distribution is required for cardiogenesis and cardiomyocyte differentiation, and point to H2Bub1 regulating tissue-specific gene expression by increasing the amount of full-length transcripts.
2023-10-31 | GSE246411 | GEO