Genome folding through loop extrusion by SMC complexes

Nature Reviews Molecular Cell Biology, Год журнала: 2021, Номер 22(7), С. 445 - 464

Опубликована: Март 25, 2021

Язык: Английский

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Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1

Nature Genetics, Год журнала: 2022, Номер 54(12), С. 1919 - 1932

Опубликована: Дек. 1, 2022

It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression most genes despite substantially perturbing three-dimensional (3D) genome folding at the level domains structural loops. To address this conundrum, we used high-resolution Micro-C nascent transcript profiling in mouse embryonic stem cells. We find that enhancer-promoter (E-P) interactions are largely insensitive to (3-h) CTCF, or WAPL. YY1 has been proposed as a regulator E-P loops, but also had minimal effects on transcription 3D folding. Strikingly, live-cell, single-molecule imaging revealed reduced factor (TF) binding chromatin. Thus, although cohesin, WAPL is not required for short-term maintenance gene expression, our results suggest may facilitate TFs search bind their targets more efficiently.

Язык: Английский

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Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation

Nature Structural & Molecular Biology, Год журнала: 2021, Номер 28(2), С. 152 - 161

Опубликована: Янв. 4, 2021

Язык: Английский

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

Nature Genetics, Год журнала: 2023, Номер 55(6), С. 1048 - 1056

Опубликована: Май 8, 2023

Язык: Английский

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Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes

Nature Structural & Molecular Biology, Год журнала: 2022, Номер 29(6), С. 563 - 574

Опубликована: Июнь 1, 2022

Abstract Developmental gene expression is often controlled by distal regulatory DNA elements called enhancers. Distant enhancer action restricted to structural chromosomal domains that are flanked CTCF-associated boundaries and formed through cohesin chromatin loop extrusion. To better understand how enhancers, genes CTCF together form control expression, we used a bottom-up approach, building series of active landscapes in inactive chromatin. We demonstrate here transcription levels activity over time reduce with increased distance. The recruits stimulate domain formation engage flanking sites formation. It requires exclusively for the activation distant genes, not proximal nearby supporting efficient long-range action. Our work supports dual model enhancers: its classic role stimulating initiation elongation from target promoters recruiting creation domains, engagement looping genes.

Язык: Английский

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BET inhibition disrupts transcription but retains enhancer-promoter contact

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Янв. 11, 2021

Abstract Enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes in higher eukaryotes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed multiple systems at loci thought to be essential for the maintenance expression. Bromodomain Extra-Terminal domain (BET) Mediator proteins have shown capable forming phase condensates super-enhancer function. Here, we show targeting cells with inhibitors BET or pharmacological degradation protein Bromodomain-containing 4 (BRD4) a strong impact on transcription but very little interactions. Dissolving reduces BRD4 binding enhancers also strongly affect transcription, without disrupting These results suggest activation separable events. Our findings further indicate dependent high levels Mediator, likely maintained by set factors including additional activator complexes and, some sites, CTCF cohesin.

Язык: 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, Год журнала: 2022, Номер 13(1)

Опубликована: Апрель 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.

Язык: Английский

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Cohesin-dependence of neuronal gene expression relates to chromatin loop length

eLife, Год журнала: 2022, Номер 11

Опубликована: Апрель 26, 2022

Cohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here, we show a prominent for cohesin the expression genes that facilitate neuronal maturation homeostasis. Unexpectedly, observed two classes activity-regulated with distinct reliance on mouse primary cortical neurons. Immediate early (IEGs) remained fully inducible by KCl BDNF, short-range enhancer-promoter contacts at IEGs

Язык: Английский

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The role of chromatin loop extrusion in antibody diversification

Nature reviews. Immunology, Год журнала: 2022, Номер 22(9), С. 550 - 566

Опубликована: Фев. 15, 2022

Язык: Английский

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

Cell Reports, Год журнала: 2023, Номер 42(4), С. 112068 - 112068

Опубликована: Апрель 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.

Язык: Английский

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