Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

Comoglio, Federico; Simonatto, Marta; Polletti, Sara; Liu, Xin; Smale, Stephen T.; Barozzi, Iros; Natoli, Gioacchino

doi:10.1101/gad.326348.119

Cited by 37 publications

(23 citation statements)

References 65 publications

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“…Hybridisation-based capture of MNase-digested DNA 51,52,[66][67][68][69] can allow selection of arbitrary genomic regions to be enriched; however, it is not readily amenable to regions containing repetitive or non-unique sequences, and it cannot separate functionally distinct alleles of the same sequence. ChIP of MNase-digested chromatin has been used to enrich nucleosomes bearing defined histone modifications 15,22,32,[70][71][72][73][74][75] ; however, this approach is unable to directly distinguish changes in nucleosome occupancies from changes in histone modification levels 15,70,72 , and it is not well-suited to map nucleosome positions surrounding non-histone targets. Finally, ATAC-seq can reveal nucleosome positions surrounding transposase-accessible genomic regions, including promoters 8,11 , and affords high levels of enrichment; however, it offers no choice of enriched regions, and mapping typically only spans a few nucleosomes surrounding active elements.…”

Section: Discussionmentioning

confidence: 99%

Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters

2020

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The organization of nucleosomes across functional genomic elements represents a critical layer of control. Here, we present a strategy for high-resolution nucleosome profiling at selected genomic features, and use this to analyse dynamic nucleosome positioning at inducible and cell-type-specific mammalian promoters. We find that nucleosome patterning at inducible promoters frequently resembles that at active promoters, even before stimulusdriven activation. Accordingly, the nucleosome profile at many inactive inducible promoters is sufficient to predict cell-type-specific responsiveness. Induction of gene expression is generally not associated with major changes to nucleosome patterning, and a subset of inducible promoters can be activated without stable nucleosome depletion from their transcription start sites. These promoters are generally dependent on remodelling enzymes for their inducible activation, and exhibit transient nucleosome depletion only at alleles undergoing transcription initiation. Together, these data reveal how the responsiveness of inducible promoters to activating stimuli is linked to cell-type-specific nucleosome patterning.

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Section: Discussionmentioning

confidence: 99%

Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters

2020

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“…While NF-κB is not thought to be a ‘pioneering factor’, i.e. a transcription factor able to initiate chromatin remodelling, evidence does support a role for the factor in changing the nucleosome landscape at activated loci [ 15 , 43 ]. The second most enriched motif in IL-1 increased accessible regions was IRF1, interferon regulatory factor 1, a factor that increases with IL-1 stimulation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

et al. 2020

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Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathwaymediated transcription factor activation and regulatory element binding. Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1). We identified 126,483 open chromatin regions, with 241 regions significantly differentially accessible following stimulation, with 64 and 177 more or less accessible, respectively. These differentially accessible regions predominantly correspond to regions of the genome marked as enhancers. Motif searching identified an overrepresentation of a number of transcription factors, most notably RelA, in the regions becoming more accessible, with analysis of ChIP-seq data confirmed RelA binding to these regions. A significant correlation in differential chromatin accessibility and gene expression was also observed. Functionality in regulating gene expression was confirmed using CRISPR/Cas9 genome-editing to delete regions that became more accessible following stimulation in the genes MMP13, IKBKE and C1QTNF1. These same regions were also accessible for activation using a dCas9-transcriptional activator and showed enhancer activity in a cellular model. Together, these data describe and functionally validate a number of dynamically accessible chromatin regions involved in inflammatory signalling.

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“…Chromatin remodeling can proceed by NF-κB-dependent and -independent pathways, as schematically shown in Figure 2 A. In the prevailing model, rapidly expressed genes, such as chemokine genes, do not require a priori nucleosome remodeling, and are often enriched in CpG-islands [ 51 , 52 ]. Today, it is still not clear if NF-κB-dependent remodeling occurs preferentially at loci displaying paused RNA polymerase II (RNAPII) complexes or at promoters which show de novo recruitment upon stimulation.…”

Section: Regulation Of Nf-κb In the Nucleusmentioning

confidence: 99%

Regulation of Transcription Factor NF-κB in Its Natural Habitat: The Nucleus

Bacher

Meier-Soelch

Schmitz

2021

Cells

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Activation of the transcription factor NF-κB elicits an individually tailored transcriptional response in order to meet the particular requirements of specific cell types, tissues, or organs. Control of the induction kinetics, amplitude, and termination of gene expression involves multiple layers of NF-κB regulation in the nucleus. Here we discuss some recent advances in our understanding of the mutual relations between NF-κB and chromatin regulators also in the context of different levels of genome organization. Changes in the 3D folding of the genome, as they occur during senescence or in cancer cells, can causally contribute to sustained increases in NF-κB activity. We also highlight the participation of NF-κB in the formation of hierarchically organized super enhancers, which enable the coordinated expression of co-regulated sets of NF-κB target genes. The identification of mechanisms allowing the specific regulation of NF-κB target gene clusters could potentially enable targeted therapeutic interventions, allowing selective interference with subsets of the NF-κB response without a complete inactivation of this key signaling system.

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Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

Cited by 37 publications

References 65 publications

Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters

Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation

Regulation of Transcription Factor NF-κB in Its Natural Habitat: The Nucleus

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