Stochastic models of nucleosome dynamics reveal regulatory rules of stimulus-induced epigenome remodeling
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ABSTRACT:
PROVIDER: PRJNA657750 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The genomic positions of nucleosomes are a defining feature of the epigenomic state and hence of cell identity. Signal-dependent transcription factors (SDTFs), upon activation, modify the positioning of nucleosomes and cause epigenome remodeling. Here, we developed Markov models of nucleosome wrapping and unwrapping, and fit them to high resolution deep sequencing data of DNA accessibility to reveal biophysical principles of nucleosome dynamics. We found that 1) the dynamics of DNA unwrapping are significantly slower in vivo than reported from in vitro experimental data, 2) there is clear evidence for cooperativity in wrapping and unwrapping, 3) SDTF activity produced highest eviction probability when its binding site is close to but not on top of the nucleosome dyad, and 4) oscillatory SDTFs produce more variability than constant SDTF activities. Our work uncovers the regulatory rules governing nucleosome dynamics in vivo, which can predict epigenomic alterations during inflammation at single nucleosome resolution.
2022-04-24 | GSE156385 | GEO
Project description:Dynamic control of the accessibility of the genomic regulatory information is at the heart of stimulus-induced gene expression changes. Whereas chromatin accessibility assays describe dynamic changes in open chromatin over time, they provide only indirect and limited information on the nucleosome remodeling events that underlie such changes. Here, we combined accessibility assays and ChIP-seq on nucleosomes generated by micrococcal nuclease digestion in resting and LPS-activated macrophages. We devised a novel quantitative framework to discriminate different types of nucleosome remodeling events and used it to analyze nucleosome organization at genomic cis-regulatory elements modulated by stimulation on a genomic scale. At typical stimulus-activated enhancers, remodeling events were commonly asymmetric, with only one of the two nucleosomes flanking the central accessible region being remodeled. A systematic analysis of nucleosome organization revealed distinct associations of individual TFs with remodeling and showed that most remodeling events tended to occur early in the response and to be maintained over time, with progressively fewer novel events occurring at later times.
2019-08-01 | GSE119691 | GEO
Project description:Dynamic control of the accessibility of the genomic regulatory information is at the heart of stimulus-induced gene expression changes. Whereas chromatin accessibility assays describe dynamic changes in open chromatin over time, they provide only indirect and limited information on the nucleosome remodeling events that underlie such changes. Here, we combined accessibility assays and ChIP-seq on nucleosomes generated by micrococcal nuclease digestion in resting and LPS-activated macrophages. We devised a novel quantitative framework to discriminate different types of nucleosome remodeling events and used it to analyze nucleosome organization at genomic cis-regulatory elements modulated by stimulation on a genomic scale. At typical stimulus-activated enhancers, remodeling events were commonly asymmetric, with only one of the two nucleosomes flanking the central accessible region being remodeled. A systematic analysis of nucleosome organization revealed distinct associations of individual TFs with remodeling and showed that most remodeling events tended to occur early in the response and to be maintained over time, with progressively fewer novel events occurring at later times.
2019-08-01 | GSE119690 | GEO
Project description:Dynamic control of the accessibility of the genomic regulatory information is at the heart of stimulus-induced gene expression changes. Whereas chromatin accessibility assays describe dynamic changes in open chromatin over time, they provide only indirect and limited information on the nucleosome remodeling events that underlie such changes. Here, we combined accessibility assays and ChIP-seq on nucleosomes generated by micrococcal nuclease digestion in resting and LPS-activated macrophages. We devised a novel quantitative framework to discriminate different types of nucleosome remodeling events and used it to analyze nucleosome organization at genomic cis-regulatory elements modulated by stimulation on a genomic scale. At typical stimulus-activated enhancers, remodeling events were commonly asymmetric, with only one of the two nucleosomes flanking the central accessible region being remodeled. A systematic analysis of nucleosome organization revealed distinct associations of individual TFs with remodeling and showed that most remodeling events tended to occur early in the response and to be maintained over time, with progressively fewer novel events occurring at later times.
2019-08-01 | GSE119692 | GEO
Project description: Not available
| S-EPMC6719622 | biostudies-literature
Project description:Protein concentrations evolve under greater evolutionary constraint than mRNA levels. In addition, translation efficiency of mRNA populations represents the chief determinant of basal protein concentrations. This raises a fundamental question as to how mRNA and protein levels are actively coordinated in dynamic systems responding to acute physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that alternative translation efficiencies, not mRNA levels, represent the major adaptive mechanism that governs the cellular response to perturbations in [O2]. This phenomenon is coordinated by eIF4F under atmospheric [O2] and the previously uncharacterized hypoxic eIF4F (eIF4FH) under low [O2]. The oxygen-regulated remodeling of translation efficiency enables oxygenated and hypoxic cells to produce surprisingly divergent translatomes of similar complexity, with minimal dependence on mRNA levels. Changes in mRNA concentrations observed between normoxic and hypoxic cells are likely neutral, as they are during evolution. We propose that mRNAs contain hard-wired translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus.
2016-02-05 | PXD003037 | Pride
Project description:Msn2-mediated nucleosome remodeling dynamics
| PRJEB4737 | ENA
Project description:Interventions: Case series:Nucleosome Complex CAR-T cells
Primary outcome(s): Tumor markers
Study Design: Sequential
| 2684952 | ecrin-mdr-crc
Project description:Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While structural and biochemical studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk surface may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome surface binding hot-spots exist remains unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that collectively disrupts all exposed histone surfaces to establish the universal principles of nucleosome binding. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk binding and are critical for the majority of nucleosome-protein interactions. In contrast, nearly half of the nucleosome disk surface participates only minimally in protein binding. In addition to establishing the fundamental principles of chromatin binding, our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation, and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly binds the acidic patch and elucidate a redundant charge-based mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub for chromatin-targeted activities and curates a list of nucleosome interacting proteins that will enable mechanistic exploration of many unexpected chromatin-templated nuclear processes.
2020-06-24 | PXD018690 | Pride
Project description:Protein concentrations evolve under greater evolutionary constraint than mRNA levels. In addition, translation efficiency of mRNA populations represents the chief determinant of basal protein concentrations. This raises a fundamental question as to how mRNA and protein levels are actively coordinated in dynamic systems responding to acute physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that alternative translation efficiencies, not mRNA levels, represent the major adaptive mechanism that governs the cellular response to perturbations in [O2]. This phenomenon is coordinated by eIF4F under atmospheric [O2] and the previously uncharacterized hypoxic eIF4F (eIF4FH) under low [O2]. The oxygen-regulated remodeling of translation efficiency enables oxygenated and hypoxic cells to produce surprisingly divergent translatomes of similar complexity, with minimal dependence on mRNA levels. Changes in mRNA concentrations observed between normoxic and hypoxic cells are likely neutral, as they are during evolution. We propose that mRNAs contain hard-wired translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus.
2016-07-20 | MSV000079962 | MassIVE