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Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (Micro-C XL)

ABSTRACT: Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (Micro-C XL)

PROVIDER: PRJNA702747 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13736654_1.fastq.gz	Fastqsanger.gz
	SRR13736654_2.fastq.gz	Fastqsanger.gz
	SRR13736655_1.fastq.gz	Fastqsanger.gz
	SRR13736655_2.fastq.gz	Fastqsanger.gz
	SRR13736656_1.fastq.gz	Fastqsanger.gz

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Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (Micro-C XL)

Project description:Determining the conformation of chromatin in cells at the nucleosome level and its relationship to cellular processes has been a central challenge in biology. We show that in quiescent yeast, widespread transcriptional repression coincides with the local compaction of chromatin fibers into structures that are less condensed and more heteromorphic than canonical 30-nanometer forms. Acetylation or substitution of H4 tail residues decompacts fibers and leads to global transcriptional de-repression. Fiber decompaction also increases the rate of loop extrusion by condensin. These findings establish a role for H4 tail-dependent local chromatin fiber folding in regulating transcription and loop extrusion in cells. They also demonstrate the physiological relevance of canonical chromatin fiber folding mechanisms even in the absence of regular 30-nanometer structures.

2021-11-04 | GSE167019 | GEO

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (ChIP-Seq)

2021-11-04 | GSE167017 | GEO

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells

Project description:Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells

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Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (ChIP-Seq)

Project description:Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (ChIP-Seq)

| PRJNA702745 | ENA

Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells.

Project description:A longstanding hypothesis is that chromatin fiber folding mediated by interactions between nearby nucleosomes represses transcription. However, it has been difficult to determine the relationship between local chromatin fiber compaction and transcription in cells. Further, global changes in fiber diameters have not been observed, even between interphase and mitotic chromosomes. We show that an increase in the range of local inter-nucleosomal contacts in quiescent yeast drives the compaction of chromatin fibers genome-wide. Unlike actively dividing cells, inter-nucleosomal interactions in quiescent cells require a basic patch in the histone H4 tail. This quiescence-specific fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin. These results reveal that global changes in chromatin fiber compaction can occur during cell state transitions, and establish physiological roles for local chromatin fiber folding in regulating transcription and chromatin domain formation.

| S-EPMC8598167 | biostudies-literature

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-11-04 | GSE167020 | GEO

Condensin-dependent chromatin condensation represses transcription globally during quiescence [Micro-C XL]

Project description:Quiescence is a stress-resistant state in which cells reversibly exit the mitotic cell cycle and suspend most cellular processes. Quiescence is essential for stem cell maintenance and its misregulation is implicated in tumor formation. One of the conserved hallmarks of quiescent cells, from Saccharomyces cerevisiae to humans, is highly condensed chromatin. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide to elucidate mechanisms and functions of condensed chromatin in quiescent S. cerevisiae cells. We describe previously uncharacterized chromatin domains on the order of 10-60 kilobases that in quiescent cells are formed by condensin-mediated chromatin loops. Conditional depletion of condensin prevents chromatin condensation during quiescence entry and leads to widespread transcriptional de-repression. We further demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts. We propose that condensin-dependent condensation of chromatin represses transcription throughout the quiescent cell genome.

2018-12-27 | GSE120605 | GEO

Micro-C XL: assaying chromosome conformation at length scales from the nucleosome to the entire genome

Project description:Structural analysis of chromosome folding in vivo has been revolutionized by Chromosome Conformation Capture (3C) and related methods, which use proximity ligation to identify chromosomal loci in physical contact. We recently described a variant 3C technique, Micro-C, in which chromatin is fragmented to mononucleosomes using micrococcal nuclease, enabling nucleosome-resolution folding maps of the genome. Here, we describe an improved Micro-C protocol using long crosslinkers, termed Micro-C XL, which exhibits greatly increased signal to noise, and provides further insight into the folding of the yeast genome. We also find that signal to noise is much improved in Micro-C XL libraries generated from relatively insoluble chromatin as opposed to soluble material, providing a simple method to physically enrich for bona-fide long-range interactions. Micro-C XL maps of the budding and fission yeast genomes reveal both short-range chromosome fiber features such as chromosomally-interacting domains (CIDs), as well as higher-order features such as clustering of centromeres and telomeres, thereby addressing the primary discrepancy between prior Micro-C data and reported 3C and Hi-C analyses. Interestingly, comparison of chromosome folding maps of S. cerevisiae and S. pombe revealed widespread qualitative similarities, yet quantitative differences, between these distantly-related species. Micro-C XL thus provides a single assay suitable for interrogation of chromosome folding at length scales from the nucleosome to the full genome.

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Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes

Project description:We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CTCF and cohesin act together to extrude loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loop in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair. in situ Hi-C and HYbrid Capture Hi-C (Hi-C2) were used to probe the three-dimensional structure of the genome in two different human cell types before and after genome editing.

2015-10-23 | E-GEOD-74072 | biostudies-arrayexpress

Cohesin-dependent chromosome loop extrusion is limited by transcription and stalled replication forks [Hi-C]

Project description:Genome function depends on regulated chromosome folding, and loop extrusion by the protein complex cohesin is essential for this multilayered organization. The chromosomal positioning of cohesin is controlled by transcription, and the complex also localizes to stalled replication forks. However, the role of transcription and replication in chromosome looping remains unclear. Here, we show that reduction of chromosome-bound RNA polymerase weakens normal cohesin loop extrusion boundaries, allowing cohesin to form new long-range chromosome cis interactions. Stress response genes activated by transcription inhibition are also shown to act as new loop extrusion boundaries. Furthermore, cohesin loop extrusion during early S-phase is jointly controlled by transcription and replication units. Together, the results reveal that replication and transcription machineries are chromosome folding regulators that block the progression of loop-extruding cohesin, opening for new perspectives on cohesin’s roles in genome function and stability.

2022-06-15 | GSE162193 | GEO

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