Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD009966
PROVIDER: PRJNA396955 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing [RNA-seq]
| PRJNA401867 | ENA
Project description:Replication-independent deposition of histone variant H3.3 into chromatin is essential for many biological processes, including development, oogenesis and nuclear reprogramming. Unlike replication-dependent H3.1/2 isoforms, H3.3 is expressed throughout the cell cycle and becomes enriched in postmitotic cells with age. However, lifelong dynamics of H3 variant replacement and the impact of this process on chromatin organization remain largely undefined. To address this, we investigated genome-wide changes in histone H3 variants composition and H3 modification abundances throughout the lifespan in mice using quantitative mass spectrometry (MS) – based middle-down proteomics strategy. Using middle-down MS we demonstrate that H3.3 accumulates in the chromatin of various somatic mouse tissues throughout life, resulting in near complete replacement of H3.1/2 isoforms by the late adulthood. Accumulation of H3.3 is associated with profound changes in the global level of H3 methylation. H3.3-containing chromatin exhibits distinct stable levels of H3R17me2 and H3K36me2, different from those on H3.1/H3.2-containing chromatin, indicating a direct link between H3 variant exchange and histone methylation dynamics with age. In summary, our study provides the first time comprehensive characterization of dynamic changes in the H3 modification landscape during mouse lifespan and links these changes to the age-dependent accumulation of histone variant H3.3.
2017-07-28 | PXD005300 | Pride
Project description:The closely related replicative H3 and non-replicative H3.3 variants show specific requirement during development in vertebrates. Whether it involves distinct mode of deposition or unique roles once incorporated into chromatin remains unclear. To disentangle the two aspects, we took advantage of the Xenopus early development combined with chromatin assays. We systematically mutated H3.3 at each four residues that differ from H3.2 and tested their ability to rescue developmental defects due to endogenous H3.3 depletion. Surprisingly, all H3.3 mutated variants functionally complemented endogenous H3.3, regardless of their incorporation pathways, except for one residue, the serine at position 31. The phosphorylation at this unique residue occurs onto chromatin with a peak in late mitosis, and depends on the networks of cell cycle kinases. Notably, while the alanine substitution failed to rescue H3.3 depletion, a phosphomimic residue sufficed. Based on proteomics studies with histone peptides and Xenopus extracts, we find that the phosphomimic histone mutant attracts transcription related factors. Furthermore, we evidence a crosstalk whereby phosphorylation on H3.3S31 favors H3.3K27ac. At gastrulation, we conclude that the critical importance of the H3.3S31 residue is independent of the variant incorporation pathway. It rather reflects a signaling role engaging key binding partners and crosstalks on neighboring amino acids. We discuss how this single evolutionary conserved residue conveys both in interphase and mitosis unique properties for this variant in vertebrates during cell cycle and cell fate commitment.
2020-03-13 | PXD016497 | Pride
Project description:Giant cell tumor of bone is a rare bone neoplasm driven by oncogenic hotspot G34W/L/V mutations in the non-canonical histone variant H3.3. This study provides primary data of genomic (WGS), transcriptomic (RNA-seq) and epigenomic (histone mark ChIP-seq, WGBS, ATAC-seq) profiling of primary GCTB samples from several cohorts in Germany and Korea. We confirm the H3.3-G34 mutations as sole genetic drivers of GCTB, and describe the epigenetic alterations in mutant GCTB stromal cells.
| EGAS00001003730 | EGA
Project description:Histone variants can effect nucleosome stability or affect histone of DNA modifications. H3.3 is a major H3 histone variant that is incorporated into chromatin outside of S-phase in various eukaryotes. In animals, H3.3 is associated with active transcription and possibly maintenance of transcriptional memory. Plant H3.3, which evolved independently of animal H3.3, is much less well understood. We performed ChIP-chip using chromatin from rosette leaves of 35S:H3.3-YFP plants.
2014-03-10 | E-MTAB-1685 | biostudies-arrayexpress
Project description:Endogenous retroviruses (ERVs) have provided an evolutionary advantage in the diversification of transcript regulation and are thought to be involved in the establishment of extraembryonic tissues during development. However, silencing of these elements remains critical for the maintenance of genome stability. Here, we define a new chromatin state that is uniquely characterized by the combination of the histone variant H3.3 and H3K9me3, two chromatin ‘marks’ that have previously been considered to belong to fundamentally opposing chromatin states. H3.3/H3K9me3 heterochromatin is fundamentally distinct from ‘canonical’ H3K9me3 heterochromatin that has been under study for decades and this unique functional interplay of a histone variant and a repressive histone mark is crucial for silencing ERVs in ESCs. Our study solidifies the emerging notion that H3.3 is not a histone variant associated exclusively with “active” chromatin and further suggests that its incorporation at unique heterochromatic regions may be central to its function during development and the maintenance of genome stability. RNA-seq analysis of three embryonic stem cell lines WT, H3.3 KO1, and H3.3 KO2)
2015-05-05 | E-GEOD-59104 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE16882: Histone H1 binding is restricted by histone variant H3.3 (Nucleosome) GSE16883: Histone H1 binding is restricted by histone variant H3.3 (DamID) GSE16884: Histone H1 binding is restricted by histone variant H3.3 (Expression) GSE19764: Histone H1 binding is restricted by histone variant H3.3 (FAIRE) Refer to individual Series
2009-10-15 | E-GEOD-16885 | biostudies-arrayexpress
Project description:While transcription as regulated by histones and their post-translational modifications have been well described, the connection between histone variants and changes to transcription remains poorly characterized. Potentially important insight into this process is provided by the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence on cellular growth behavior, gene expression, and chromatin compaction. The primary cells with G34W show increased colony formation, infiltration and proliferation, hallmarks in aggressive tumor development. Isogenic cell lines with G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and biopsies suggest that most genes are downregulated, which is also reflected in increased chromatin compaction. We identified components of the spliceosome complex specifically interacting with G34W in established isogenic cell lines with a GFP-tagged H3.3. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role in RNA processing and chromatin modulation that is blocked by G34W, potentially driving the tumorigenic process in GCTB.
2017-10-18 | GSE103559 | GEO
Project description:While transcription as regulated by histones and their post-translational modifications have been well described, the connection between histone variants and changes to transcription remains poorly characterized. Potentially important insight into this process is provided by the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence on cellular growth behavior, gene expression, and chromatin compaction. The primary cells with G34W show increased colony formation, infiltration and proliferation, hallmarks in aggressive tumor development. Isogenic cell lines with G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and biopsies suggest that most genes are downregulated, which is also reflected in increased chromatin compaction. We identified components of the spliceosome complex specifically interacting with G34W in established isogenic cell lines with a GFP-tagged H3.3. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role in RNA processing and chromatin modulation that is blocked by G34W, potentially driving the tumorigenic process in GCTB.
2017-10-18 | GSE102193 | GEO
Project description:In this study, we have uncovered novel proteolytic processing of the histone H3 tail in senescence models in primary fibroblasts and melanocytes. Cleavage of H3 tail occurs at two distinct residues and is mediated by Cathepsin L. We show that variant H3.3 is preferentially cleaved, and that cleaved histones are associated with chromatin and incorporated into nucleosomes. We also found that the histone chaperone ASF1a is required for chromatin incorporation of the cleaved histone species. Further, we show that overexpression of cleaved H3.3 induces a senescence program in fibroblasts in the absensence of oncogenic signaling.
2014-10-01 | GSE55949 | GEO