Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment
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ABSTRACT:
PROVIDER: PRJNA550123 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10325906_1.fastq.gz | Fastqsanger.gz | |||
| SRR10325906_2.fastq.gz | Fastqsanger.gz | |||
| SRR10325907_1.fastq.gz | Fastqsanger.gz | |||
| SRR10325907_2.fastq.gz | Fastqsanger.gz | |||
| SRR10325908_1.fastq.gz | Fastqsanger.gz |
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Project description:Delineating how chromosomes fold at length scales beyond one megabase remains obscure relative to smaller-scale folding into TADs, loops, and nucleosomes. We find that rather than simply unfolding chromatin, histone hyperacetylation results in interactions between distant genomic loci separated by tens to hundreds of megabases, even in the absence of transcription. These hyperacetylated "megadomains" are formed by the BRD4-NUT fusion oncoprotein, interact both within and between chromosomes, and form a specific nuclear subcompartment that has elevated gene activity with respect to other subcompartments. Pharmacological degradation of BRD4-NUT results in collapse of megadomains and attenuation of the interactions between them. In contrast, these interactions persist and contacts between newly acetylated regions are formed after inhibiting RNA polymerase II initiation. Our structure-function approach thus reveals that broad chromatin domains of identical biochemical composition, independent of transcription, form nuclear subcompartments, and also indicates the potential of altering chromosome structure for treating human disease.
| S-EPMC7164681 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-01 | GSE133165 | GEO
Project description:We describe a Hi-C based method, Micro-C, in which micrococcal nuclease is used instead of restriction enzymes to fragment chromatin, enabling nucleosome resolution chromosome folding maps. Analysis of Micro-C maps for budding yeast reveals abundant self-associating domains similar to those reported in other species, but not previously observed in yeast. These structures, far shorted than topologically-associating domains in mammals, typically encompass one to five genes in yeast. Strong boundaries between self-associating domains occur at promoters of highly transcribed genes, and regions of rapid histone turnover that are typically bound by the RSC chromatin-remodeling complex. Investigation of chromosome folding in mutants confirms roles for RSC, “gene looping” factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and N-terminal tail of H4 in folding of the yeast genome. This approach provides detailed structural maps of a eukaryotic genome and our findings provide insights into the machinery underlying chromosome compaction. Chromatin is fragmented by Mnase, subsequenct nucleosomal end repair, and a modified two-step method for purfiying ligation products. Using Illumina paired-end sequencing maps Micro-C library and generates nucleosome resolution contact maps. The readme.txt file contains additional description of how each processed data file was generated.
2015-06-25 | E-GEOD-68016 | biostudies-arrayexpress
Project description:We describe a Hi-C based method, Micro-C, in which micrococcal nuclease is used instead of restriction enzymes to fragment chromatin, enabling nucleosome resolution chromosome folding maps. Analysis of Micro-C maps for budding yeast reveals abundant self-associating domains similar to those reported in other species, but not previously observed in yeast. These structures, far shorted than topologically-associating domains in mammals, typically encompass one to five genes in yeast. Strong boundaries between self-associating domains occur at promoters of highly transcribed genes, and regions of rapid histone turnover that are typically bound by the RSC chromatin-remodeling complex. Investigation of chromosome folding in mutants confirms roles for RSC, “gene looping” factor Ssu72, Mediator, H3K56 acetyltransferase Rtt109, and N-terminal tail of H4 in folding of the yeast genome. This approach provides detailed structural maps of a eukaryotic genome and our findings provide insights into the machinery underlying chromosome compaction.
2015-06-25 | GSE68016 | GEO
Project description:Here we describe the principles of 3D genome folding dynamics in vertebrates and show how lineage-specific patterns of genome reshuffling can result in different chromatin configurations. We (i) identified different patterns of chromosome folding across vertebrate species, (ii) reconstructed ancestral marsupial and afrotherian genomes analyzing whole-genome sequences of 10 species representative of the major therian phylogroups, (iii) detected lineage-specific chromosome rearrangements and (iv) identified the dynamics of the structural properties of genome reshuffling through therian evolution.
2022-12-08 | GSE206075 | GEO
Project description:NUT, nuclear protein in testis is the universal fusion partner of BRD4 in the highly aggressive NUT Midline Carcinoma (NMC), but its physiological function is unknown. Here we show that Nut is exclusively expressed in post-meiotic spermatogenic cells, at the time of genome-wide histone hyperacetylation. Inactivation of Nut induces a spermatogenesis arrest at the histone-to-protamine replacement stage, leading to male infertility. Subsequent molecular investigations show that Nut sustains global histone H4 hyperacetylation in post-meiotic cells. Additionally, Nut mediates a p300/CBP-dependent gene expression program and, by enhancing acetylation of H4 at both K5 and K8 sites, provides binding sites for the first bromodomain of Brdt, which drives histone removal. Our results bring the first evidence of Nut’s function in spermatogenic cells where it uses the ubiquitous HATs p300/CBP to direct a cell-type specific histone H4 hyperacetylation. The ectopic activity of Nut in NMC recreates a forced p300-induced histone hyperacetylation / bromodomain-binding loop that normally operates in post-meiotic spermatogenic cells.
2018-10-15 | GSE111931 | GEO
Project description:Sepsis-induced liver dysfunction is a frequent event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification (PTM) and diseases is challenging. We studied the relationship among the lysine acetylation (Kac), the sirtuin (SIRTs), and their interactors carefully selected in sepsis-induced liver dysfunction (SILD), per-formed on LPS-stimulated HepG2 cells. Protein hyperacetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1,449 Kac sites based on comparative acetylome analysis, and quantified 1,086 Kac sites on 410 proteins for acetylation. Interestingly, the up-regulated Kac proteins are enriched in glycolysis/gluconeogenesis pathways in the KEGG category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed in three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, increasing the lactate concentration as a result. In conclusion, this study is the first to conduct global profiling of Kac, suggesting the Kac mecha-nism of PKM2 in glycolysis of sepsis. Moreover, it helps further understand the systematical in-formation of hyperacetylation during the sepsis process.
2024-01-30 | PXD027496 | Pride
Project description:Histone deacetylase inhibitors (HDACis) have been shown to potentiate hippocampal-dependent memory and synaptic plasticity and to ameliorate cognitive deficits and degeneration in animal models for different neuropsychiatric conditions. However, the impact of these drugs on hippocampal histone acetylation and gene expression profiles at the genomic level, and the molecular mechanisms that underlie their specificity and beneficial effects in neural tissue, remains obscure. Here, we mapped four relevant histone marks (H3K4me3, AcH3K9,14, AcH4K12 and pan-AcH2B) in hippocampal chromatin and investigated at the whole-genome level the impact of HDAC inhibition on acetylation profiles and basal and activity-driven gene expression. HDAC inhibition caused a dramatic histone hyperacetylation that was largely restricted to active loci pre-marked with H3K4me3 and AcH3K9,14. In addition, the comparison of Chromatin immunoprecipitation sequencing and gene expression profiles indicated that Trichostatin A-induced histone hyperacetylation, like histone hypoacetylation induced by histone acetyltransferase deficiency, had a modest impact on hippocampal gene expression and did not affect the transient transcriptional response to novelty exposure. However, HDAC inhibition caused the rapid induction of a homeostatic gene program related to chromatin deacetylation. These results illuminate both the relationship between hippocampal gene expression and histone acetylation and the mechanism of action of these important neuropsychiatric drugs. Examination of 4 different histone modifications in the hippocampus of vehicle (DMSO/Saline) or HDACi TSA (2.4 mg/kg)-treated mice. Samples were obtained 30 min after intraperitoneal administration of either TSA or Vehicle. NOTE: The ChIPseq experiments described here and those presented in the series GSE44854 were performed in paralell. Therefore, some control samples are part of both datasets (GSM1062434, GSM1062437, GSM1062441 and GSM1062442).
2013-07-09 | E-GEOD-43439 | biostudies-arrayexpress
Project description:Early biofilm forming bacteria Metagenome
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Project description:Mitochondrial proteomics was used to identify energy metabolic derangements that occur during the early stages of heart failure in well-defined mouse models. Levels of β-hydroxybutyrate dehydrogenase 1 (BDH1), a key enzyme in ketone oxidation, was upregulated. 13C-substrate flux studies and metabolomic profiling confirmed that the hypertrophied and early stage failing heart shifts to ketone bodies as a fuel source in the context of reduced oxidation of fatty acids, the chief substrate for the normal heart. This fuel shift is associated with an expansion of the acetyl pool and reduced levels of NAD+ levels resulting in increased mitochondrial protein acetylation. Myocardium of humans with heart failure also exhibited mitochondrial protein hyperacetylation. We propose that a shift to ketones as a fuel source leads to maladaptive bioenergetic consequences during the development of heart failure.
2016-02-26 | PXD001652 | Pride