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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Liquid–liquid phase separation drives cellular function and dysfunction in cancer

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(4), P. 239 - 252

Published: Feb. 11, 2022

Language: Английский

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Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(6), P. 1048 - 1056

Published: May 8, 2023

Language: Английский

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The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

Genes & Development, Journal Year: 2021, Volume and Issue: 36(1-2), P. 7 - 16

Published: Dec. 30, 2021

How distal cis -regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position another along chromosome is a biophysical puzzle—one that needs be revisited in light recent data cannot easily fit into previous solutions. Here we propose new model diverges textbook enhancer–promoter looping paradigm offer synthesis literature make case for its plausibility, focusing on coactivator p300.

Language: Английский

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Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 19, 2022

Abstract Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated cohesin CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale to what extent fine-scale regulatory interactions depend on extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, has enabled us generate the most detailed local interaction data date (20 bp resolution) precisely investigate effects of CTCF depletion architecture. Our reveal that cis -regulatory elements have distinct internal nano-scale structures, insulation dependent CTCF, but independent cohesin. In contrast, find causes a subtle reduction in longer-range enhancer-promoter can cause rewiring contacts. Together, our show not essential for interactions, contributes their robustness specificity precise regulation gene expression.

Language: Английский

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3D enhancer-promoter interactions and multi-connected hubs: Organizational principles and functional roles

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112068 - 112068

Published: April 1, 2023

The spatiotemporal control of gene expression is dependent on the activity cis-acting regulatory sequences, called enhancers, which regulate target genes over variable genomic distances and, often, by skipping intermediate promoters, suggesting mechanisms that enhancer-promoter communication. Recent genomics and imaging technologies have revealed highly complex interaction networks, whereas advanced functional studies started interrogating forces behind physical communication among multiple enhancers promoters. In this review, we first summarize our current understanding factors involved in communication, with a particular focus recent papers new layers complexities to old questions. second part subset connected "hubs" discuss their potential functions signal integration regulation, as well putative might determine dynamics assembly.

Language: Английский

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RNA polymerase II dynamics shape enhancer–promoter interactions

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(8), P. 1370 - 1380

Published: July 10, 2023

Language: Английский

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Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 280 - 290

Published: Jan. 30, 2023

Language: Английский

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CTCF shapes chromatin structure and gene expression in health and disease

EMBO Reports, Journal Year: 2022, Volume and Issue: 23(9)

Published: Aug. 22, 2022

Language: Английский

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Pairtools: from sequencing data to chromosome contacts

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 15, 2023

Abstract The field of 3D genome organization produces large amounts sequencing data from Hi-C and a rapidly-expanding set other chromosome conformation protocols (3C+). Massive heterogeneous 3C+ require high-performance flexible processing sequenced reads into contact pairs. To meet these challenges, we present pairtools – suite tools for extraction data. Pairtools provides modular command-line interface (CLI) that can be flexibly chained pipelines. both crucial core as well auxiliary building feature-rich pipelines, including pair manipulation, filtration, quality control. Benchmarking against popular pipelines shows advantages analysis. Finally, protocol-specific multi-way contacts, haplotype-resolved single-cell Hi-C. combination CLI tight integration with Python analysis libraries makes versatile foundation broad range

Language: Английский

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