Genome folding through loop extrusion by SMC complexes

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(7), P. 445 - 464

Published: March 25, 2021

Language: Английский

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Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging

Science, Journal Year: 2022, Volume and Issue: 376(6592), P. 496 - 501

Published: April 14, 2022

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF loop-extruding cohesins, but the live dynamics of loop formation stability remain unknown. Here, we directly visualized chromatin looping at

Language: Английский

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The relationship between genome structure and function

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(3), P. 154 - 168

Published: Nov. 24, 2020

Language: Английский

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Chromosome Conformation Capture and Beyond: Toward an Integrative View of Chromosome Structure and Function

Molecular Cell, Journal Year: 2020, Volume and Issue: 77(4), P. 688 - 708

Published: Jan. 27, 2020

Language: Английский

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Loop extrusion: theory meets single-molecule experiments

Current Opinion in Cell Biology, Journal Year: 2020, Volume and Issue: 64, P. 124 - 138

Published: June 1, 2020

Language: Английский

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Transcription shapes 3D chromatin organization by interacting with loop extrusion

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(11)

Published: March 10, 2023

Cohesin folds mammalian interphase chromosomes by extruding the chromatin fiber into numerous loops. "Loop extrusion" can be impeded chromatin-bound factors, such as CTCF, which generates characteristic and functional organization patterns. It has been proposed that transcription relocalizes or interferes with cohesin active promoters are loading sites. However, effects of on have not reconciled observations extrusion cohesin. To determine how modulates extrusion, we studied mouse cells in could alter abundance, dynamics, localization genetic "knockouts" regulators CTCF Wapl. Through Hi-C experiments, discovered intricate, cohesin-dependent contact patterns near genes. Chromatin around genes exhibited hallmarks interactions between transcribing RNA polymerases (RNAPs) cohesins. These reproduced polymer simulations RNAPs were moving barriers to obstructed, slowed, pushed The predicted preferential at is inconsistent our experimental data. Additional ChIP-seq experiments showed putative loader Nipbl predominantly enriched promoters. Therefore, propose preferentially loaded barrier function RNAP accounts for accumulation Altogether, find an stationary, but rather, translocates Loop might interact dynamically generate maintain gene regulatory elements shape genomic organization.

Language: Английский

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Cohesin mediates DNA loop extrusion by a “swing and clamp” mechanism

Cell, Journal Year: 2021, Volume and Issue: 184(21), P. 5448 - 5464.e22

Published: Oct. 1, 2021

Structural maintenance of chromosomes (SMC) complexes organize genome topology in all kingdoms life and have been proposed to perform this function by DNA loop extrusion. How process works is unknown. Here, we analyzed how extrusion mediated human cohesin-NIPBL complexes, which enable chromatin folding interphase cells. We identified binding sites large-scale conformational changes that are required for determined these coordinated. Our results suggest translocated a spontaneous 50 nm-swing cohesin's hinge, hands over the ATPase head SMC3, where upon ATP, clamped NIPBL. During process, NIPBL "jumps ship" from hinge toward SMC3 might thereby couple swing ATP-dependent clamping. These reveal mechanistic principles possibly other SMC mediate

Language: Английский

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MCM complexes are barriers that restrict cohesin-mediated loop extrusion

Nature, Journal Year: 2022, Volume and Issue: 606(7912), P. 197 - 203

Published: May 18, 2022

Abstract Eukaryotic genomes are compacted into loops and topologically associating domains (TADs) 1–3 , which contribute to transcription, recombination genomic stability 4,5 . Cohesin extrudes DNA that thought lengthen until CTCF boundaries encountered 6–12 Little is known about whether loop extrusion impeded by DNA-bound machines. Here we show the minichromosome maintenance (MCM) complex a barrier restricts in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture) of mouse zygotes reveals MCM loading reduces CTCF-anchored decreases TAD boundary insulation, suggests before reaching CTCF. This effect extends HCT116 cells, MCMs affect number gene expression. Simulations suggest abundant, randomly positioned partially permeable barriers. Single-molecule imaging shows physical barriers frequently constrain cohesin translocation vitro. Notably, chimeric yeast contain cohesin-interaction motif from human MCM3 induce pausing, indicating ‘active’ with binding sites. These findings raise possibility can arrive at MCMs, determine sites sister chromatid cohesion established. On basis vivo, silico vitro data, conclude distinct shape three-dimensional genome.

Language: Английский

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SMC complexes can traverse physical roadblocks bigger than their ring size

Cell Reports, Journal Year: 2022, Volume and Issue: 41(3), P. 111491 - 111491

Published: Oct. 1, 2022

Ring-shaped structural maintenance of chromosomes (SMC) complexes like condensin and cohesin extrude loops DNA. It remains, however, unclear how they can DNA in chromatin that is bound with proteins. Here, we use vitro single-molecule visualization to show nucleosomes, RNA polymerase, dCas9 pose virtually no barrier loop extrusion by yeast condensin. We find even DNA-bound nanoparticles as large 200 nm, much bigger than the SMC ring size, also translocate into during cohesin. This occurs for a single-chain version which ring-forming subunits are covalently linked cannot open entrap The data SMC-driven has surprisingly little difficulty accommodating roadblocks loop. findings extruded does not pass through (pseudo)topologically, hence pointing nontopological mechanism extrusion.

Language: Английский

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CTCF is a DNA-tension-dependent barrier to cohesin-mediated loop extrusion

Nature, Journal Year: 2023, Volume and Issue: 616(7958), P. 822 - 827

Published: April 19, 2023

Abstract In eukaryotes, genomic DNA is extruded into loops by cohesin 1 . By restraining this process, the DNA-binding protein CCCTC-binding factor (CTCF) generates topologically associating domains (TADs) 2,3 that have important roles in gene regulation and recombination during development disease 1,4–7 How CTCF establishes TAD boundaries to what extent these are permeable unclear 8 Here, address questions, we visualize interactions of single molecules on vitro. We show sufficient block diffusing cohesin, possibly reflecting how cohesive accumulates at boundaries, also loop-extruding boundaries. functions asymmetrically, as predicted; however, dependent tension. Moreover, regulates cohesin’s loop-extrusion activity changing its direction inducing loop shrinkage. Our data indicate not, previously assumed, simply a barrier cohesin-mediated extrusion but an active regulator whereby permeability can be modulated These results reveal mechanistic principles controls genome architecture.

Language: Английский

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