Predicting scale-dependent chromatin polymer properties from systematic coarse-graining DOI Creative Commons
Sangram Kadam, Kiran Kumari, Vinoth Manivannan

et al.

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

Published: July 11, 2023

Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, nature of inter-bead potentials unknown. Using nucleosome-resolution contact probability (Micro-C) data, we systematically coarse-grain predict quantities essential representation chromatin. We compute size distributions beads different coarse-graining scales, quantify fluctuations bond lengths between neighboring regions, derive effective spring constant values. Unlike prevalent notion, our findings argue that must be considered as soft particles can overlap, an potential overlap parameter. also angle giving insights into intrinsic folding local bendability While nucleosome-linker DNA naturally emerges from work, show two populations structural states. The sizes, lengths, angles mean behavior at Topologically Associating Domain (TAD) boundaries TAD interiors. integrate a model provide quantitative estimates all parameters, which serve foundational basis future simulations.

Language: Английский

Genome folding through loop extrusion by SMC complexes DOI
Iain F. Davidson, Jan‐Michael Peters

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

Published: March 25, 2021

Language: Английский

Citations

407
Understanding 3D genome organization by multidisciplinary methods DOI
Ivana Jerković, Giacomo Cavalli

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(8), P. 511 - 528

Published: May 5, 2021

Language: Английский

Citations

304
Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1 DOI Creative Commons
Tsung-Han S. Hsieh, Claudia Cattoglio, Elena Slobodyanyuk

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(12), P. 1919 - 1932

Published: Dec. 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.

Language: Английский

Citations

251
Cohesin and CTCF control the dynamics of chromosome folding DOI Creative Commons
Pia Mach, Pavel Kos, Yinxiu Zhan

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(12), P. 1907 - 1918

Published: Dec. 1, 2022

In mammals, interactions between sequences within topologically associating domains enable control of gene expression across large genomic distances. Yet it is unknown how frequently such contacts occur, long they last and depend on the dynamics chromosome folding loop extrusion activity cohesin. By imaging chromosomal locations at high spatial temporal resolution in living cells, we show that are transient occur during course a cell cycle. Interactions become more frequent longer presence convergent CTCF sites, resulting suppression variability time. Supported by physical models dynamics, our data suggest CTCF-anchored loops around 10 min. Our results long-range transcriptional regulation might rely proximity, cohesin stabilize highly dynamic structures, facilitating selected subsets interactions.

Language: Английский

Citations

185
Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning DOI Creative Commons
Elizabeth Ing‐Simmons, Roshan Vaid, Xinyang Bing

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(4), P. 487 - 499

Published: April 1, 2021

Abstract The relationship between chromatin organization and gene regulation remains unclear. While disruption of domains domain boundaries can lead to misexpression developmental genes, acute depletion regulators genome has a relatively small effect on expression. It is therefore uncertain whether expression state drive or changes in facilitate cell-type-specific activation Here, using the dorsoventral patterning Drosophila melanogaster embryo as model system, we provide evidence for independence We define tissue-specific enhancers link them patterns single-cell RNA-seq. Surprisingly, despite states expression, largely maintained across tissues. Our results indicate that conformation not necessary but rather acts scaffold facilitating when become active.

Language: Английский

Citations

137
The spatial organization of transcriptional control DOI
Antonina Hafner, Alistair N. Boettiger

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(1), P. 53 - 68

Published: Sept. 14, 2022

Language: Английский

Citations

119
Liquid–Liquid Phase Separation in Chromatin DOI Open Access
Karsten Rippe

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(2), P. a040683 - a040683

Published: June 14, 2021

Karsten Rippe Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, 69120 Heidelberg, Germany Correspondence: Karsten.Rippe{at}dkfz.de

Language: Английский

Citations

110
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF DOI Creative Commons
Abrar Aljahani, Hua Peng, Magdalena A. Karpińska

et al.

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

Citations

95
Loop stacking organizes genome folding from TADs to chromosomes DOI
Antonina Hafner, Minhee Park, Scott E. Berger

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(9), P. 1377 - 1392.e6

Published: May 1, 2023

Language: Английский

Citations

72
TADs: Dynamic structures to create stable regulatory functions DOI Creative Commons
José A. da Costa-Nunes, Daan Noordermeer

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 81, P. 102622 - 102622

Published: June 9, 2023

Language: Английский

Citations

47