Genome-wide absolute quantification of chromatin looping

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

3D genomics methods such as Hi-C and Micro-C have uncovered chromatin loops across the genome linked these to gene regulation. However, only measure interaction probabilities on a relative scale. Here, we overcome this limitation by using live imaging data calibrate in mouse embryonic stem cells, thus obtaining absolute looping for 36,804 genome. We find that looped state is generally rare, with mean probability of 2.3% maximum 26% quantified loops. On average, CTCF-CTCF are stronger than between cis-regulatory elements (3.2% vs. 1.1%). Our findings can be extended human cells differentiated under certain assumptions. Overall, establish an approach genome-wide loop quantification report occur low probabilities, generalizing recent results whole

Язык: Английский

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Engineering 3D genome organization

Nature Reviews Genetics, Год журнала: 2021, Номер 22(6), С. 343 - 360

Опубликована: Фев. 8, 2021

Язык: Английский

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Arsenic-induced epigenetic changes in cancer development

Seminars in Cancer Biology, Год журнала: 2021, Номер 76, С. 195 - 205

Опубликована: Март 30, 2021

Язык: Английский

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Spatial Features and Functional Implications of Plant 3D Genome Organization

Annual Review of Plant Biology, Год журнала: 2022, Номер 73(1), С. 173 - 200

Опубликована: Фев. 7, 2022

The advent of high-throughput sequencing-based methods for chromatin conformation, accessibility, and immunoprecipitation assays has been a turning point in 3D genomics. Altogether, these new tools have pushing upward the interpretation pioneer cytogenetic evidence higher order packing. Here, we review latest development our understanding plant spatial genome structures different levels organization discuss their functional implications. Then, spotlight complexity organellar (i.e., mitochondria plastids) genomes packing into nucleoids. Finally, propose unaddressed research axes to investigate links between chromatin-like dynamics transcriptional regulation within

Язык: Английский

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Full circle: a brief history of cohesin and the regulation of gene expression

FEBS Journal, Год журнала: 2022, Номер 290(7), С. 1670 - 1687

Опубликована: Янв. 20, 2022

The cohesin complex has a range of crucial functions in the cell. Cohesin is essential for mediating chromatid cohesion during mitosis, repair double‐strand DNA breaks, and control gene transcription. This last function been subject intense research ever since discovery cohesin's role long‐range regulation cut Drosophila. Subsequent showed that expression some genes exquisitely sensitive to depletion, while others remain relatively unperturbed. Sensitivity depletion also remarkably cell type‐ and/or condition‐specific. recent integral forming chromatin loops via loop extrusion should explain much regulatory properties, but surprisingly, failed identify ‘one size fits all’ mechanism how controls expression. review will illustrate early examples cohesin‐dependent integrate with later work on genome organization mechanisms by which regulates

Язык: Английский

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Theory of chromatin organization maintained by active loop extrusion

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(23)

Опубликована: Май 30, 2023

The active loop extrusion hypothesis proposes that chromatin threads through the cohesin protein complex into progressively larger loops until reaching specific boundary elements. We build upon this and develop an analytical theory for which predicts formation probability is a nonmonotonic function of length describes contact probabilities. validate our model with Monte Carlo hybrid Molecular Dynamics-Monte simulations demonstrate recapitulates experimental conformation capture data. Our results support as mechanism organization provide description may be used to specifically modify

Язык: Английский

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DNA double-strand break end synapsis by DNA loop extrusion

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 6, 2023

Abstract DNA double-strand breaks (DSBs) occur every cell cycle and must be efficiently repaired. Non-homologous end joining (NHEJ) is the dominant pathway for DSB repair in G1-phase. The first step of NHEJ to bring two ends back into proximity (synapsis). Although synapsis generally assumed through passive diffusion, we show that diffusion unlikely produce speed observed cells. Instead, hypothesize loop extrusion facilitates synapsis. By combining experimentally constrained simulations theory, a simple model by previous live-cell imaging data only modestly accelerates an expanded with targeted loading extruding factors (LEFs), small portion long-lived LEFs, LEF stabilization boundary elements achieves fast near 100% efficiency. We propose contributes mediating

Язык: Английский

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Cis-regulatory chromatin contacts form de novo in the absence of loop extrusion

Опубликована: Янв. 13, 2025

SUMMARY NIPBL promotes chromatin loop extrusion by the cohesin complex until it stalls at convergently oriented CTCF sites, leading to formation of structural loops. However, what extent contributes establishment vs maintenance cis -regulatory element (CRE) connectivity is poorly understood. Here, we explored de novo folding patterns mitosis-to-G1-phase transition upon acute loss. depletion primarily impaired cohesin-mediated loops with dependence being proportional length. In contrast, majority CRE were established independently regardless slowed re-formation weak enhancers. Transcription genes NIPBL-independent anchors was activated normally in absence NIPBL. sum, most regulatory contacts and gene transcription following mitotic exit independent extrusion.

Язык: Английский

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Convergent pairs of highly transcribed genes restrict chromatin looping in Dictyostelium discoideum

Nucleic Acids Research, Год журнала: 2025, Номер 53(2)

Опубликована: Янв. 6, 2025

Abstract Dictyostelium discoideum is a unicellular slime mold, developing into multicellular fruiting body upon starvation. Development accompanied by large-scale shifts in gene expression program, but underlying features of chromatin spatial organization remain unknown. Here, we report that the 3D genome organized positionally conserved, largely consecutive, non-hierarchical and weakly insulated loops at onset development. The transcription level within loop interior tends to be higher than adjacent regions. Loop interiors frequently contain functionally linked genes which coherently change during anchors are predominantly positioned convergent orientation. Results polymer simulations Hi-C-based observations suggest profile may arise from interplay between extrusion-driven folding. In this scenario, pair serves as bidirectional extrusion barrier or ‘diode’ controls passage cohesin extruder relative paired genes.

Язык: Английский

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Regulation of 3D chromatin organization by CTCF

Current Opinion in Genetics & Development, Год журнала: 2020, Номер 67, С. 33 - 40

Опубликована: Ноя. 28, 2020

Язык: Английский

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