Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors DOI Creative Commons
Ryuichiro Nakato,

Toyonori Sakata,

Jiankang Wang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 19, 2023

Abstract Cohesin regulates gene expression through context-specific chromatin folding mechanisms such as enhancer–promoter looping and topologically associating domain (TAD) formation by cooperating with factors cohesin loaders the insulation factor CTCF. We developed a computational workflow to explore how three-dimensional (3D) structure are regulated collectively or individually related factors. The main component is CustardPy, which multi-omics datasets compared systematically. To validate our methodology, we generated 3D genome, transcriptome, epigenome data before after depletion of effects depletion. observed diverse on genome changes were correlated splitting TADs caused loss. also variations in long-range interactions across TADs, their epigenomic states. These tools will be valuable for studies.

Language: Английский

Genome-wide absolute quantification of chromatin looping DOI Creative Commons
James M. Jusuf, Simon Grosse‐Holz, Michele Gabriele

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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

Language: Английский

Citations

1
Engineering 3D genome organization DOI
Haifeng Wang, Mengting Han, Lei S. Qi

et al.

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(6), P. 343 - 360

Published: Feb. 8, 2021

Language: Английский

Citations

51
Arsenic-induced epigenetic changes in cancer development DOI
Wesley N. Saintilnord, Yvonne Fondufe‐Mittendorf

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 76, P. 195 - 205

Published: March 30, 2021

Language: Английский

Citations

43
Spatial Features and Functional Implications of Plant 3D Genome Organization DOI
Katherine Domb, Nan Wang, Guillaume Hummel

et al.

Annual Review of Plant Biology, Journal Year: 2022, Volume and Issue: 73(1), P. 173 - 200

Published: Feb. 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

Language: Английский

Citations

36
Full circle: a brief history of cohesin and the regulation of gene expression DOI Creative Commons
Julia A. Horsfield

FEBS Journal, Journal Year: 2022, Volume and Issue: 290(7), P. 1670 - 1687

Published: Jan. 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

Language: Английский

Citations

33
Theory of chromatin organization maintained by active loop extrusion DOI Creative Commons
Brian Chan, Michael Rubinstein

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(23)

Published: May 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

Language: Английский

Citations

22
DNA double-strand break end synapsis by DNA loop extrusion DOI Creative Commons
Jin Yang, Hugo B. Brandão, Anders S. Hansen

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 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

Language: Английский

Citations

19
LDB1 establishes multi-enhancer networks to regulate gene expression DOI
Nicholas Aboreden, Jessica Lam, Viraat Y. Goel

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

8
Regulation of 3D chromatin organization by CTCF DOI
Jian‐Feng Xiang, Victor G. Corces

Current Opinion in Genetics & Development, Journal Year: 2020, Volume and Issue: 67, P. 33 - 40

Published: Nov. 28, 2020

Language: Английский

Citations

49
The macro and micro of chromosome conformation capture DOI Creative Commons
Viraat Y. Goel, Anders S. Hansen

Wiley Interdisciplinary Reviews Developmental Biology, Journal Year: 2020, Volume and Issue: 10(6)

Published: Sept. 28, 2020

Abstract The 3D organization of the genome facilitates gene regulation, replication, and repair, making it a key feature genomic function one that remains to be properly understood. Over past two decades, variety chromosome conformation capture (3C) methods have delineated folding from megabase‐scale compartments topologically associating domains (TADs) down kilobase‐scale enhancer‐promoter interactions. Understanding functional role each layer is gateway understanding cell state, development, disease. Here, we discuss evolution 3C‐based technologies for mapping organization. We focus on genomics provide historical account development 3C Hi‐C. also ChIP‐based techniques mediated by specific proteins, capture‐based particular regions or regulatory elements, 3C‐orthogonal do not rely restriction digestion proximity ligation, DNA–RNA RNA–RNA interactomes. consider biological discoveries come these methods, examine mechanistic contributions CTCF, cohesin, loop extrusion folding, detail field's current nuclear architecture. Finally, give special consideration Micro‐C as an emerging frontier in recent findings uncovering fine‐scale chromatin unprecedented detail. This article categorized under: Gene Expression Transcriptional Hierarchies > Regulatory Mechanisms Networks Genomics

Language: Английский

Citations

42