Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription DOI Creative Commons
Kathleen S Metz Reed, Eric S. Davis, Marielle L. Bond

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 41(5), P. 111567 - 111567

Published: Nov. 1, 2022

To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers genes connected by loops exhibit stronger correlations histone H3K27 acetylation expression than can be explained genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes at distal enhancers precede expression. Changes directional bias differential loop anchors; gained are associated with increased oriented away from the center loop, lost often accompanied high levels transcription within boundaries themselves. These results consistent reciprocal relationship where facilitate connecting promoters to whereas impede formation.

Language: Английский

Enhancer–promoter contact formation requires RNAPII and antagonizes loop extrusion DOI
Shu Zhang, Nadine Übelmesser,

Mariano Barbieri

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(5), P. 832 - 840

Published: April 3, 2023

Language: Английский

Citations

110

Transcription regulation by long non-coding RNAs: mechanisms and disease relevance DOI
Jorge Ferrer, Nadya Dimitrova

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(5), P. 396 - 415

Published: Jan. 19, 2024

Language: Английский

Citations

91

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

Christopher M Uyehara,

Effie Apostolou

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

Citations

81

CTCF and R-loops are boundaries of cohesin-mediated DNA looping DOI Creative Commons
Hongshan Zhang, Zhubing Shi, Edward J. Banigan

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(16), P. 2856 - 2871.e8

Published: Aug. 1, 2023

Language: Английский

Citations

52

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

45

Boundary stacking interactions enable cross-TAD enhancer–promoter communication during limb development DOI
Tzu-Chiao Hung, David M. Kingsley, Alistair N. Boettiger

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(2), P. 306 - 314

Published: Jan. 18, 2024

Language: Английский

Citations

30

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils DOI Creative Commons
Kristian Jeppsson, Biswajit Pradhan, Takashi Sutani

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(5), P. 867 - 882.e5

Published: Jan. 30, 2024

The structural maintenance of chromosomes (SMC) protein complexes—cohesin, condensin, and the Smc5/6 complex (Smc5/6)—are essential for chromosome function. At molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates loops in interphase, condensin compacts mitotic chromosomes. However, role Smc5/6's recently discovered extrusion activity is unknown. Here, we uncover that associates with transcription-induced positively supercoiled at cohesin-dependent boundaries on budding yeast (Saccharomyces cerevisiae) Mechanistically, single-molecule imaging reveals dimers specifically recognize tip plectonemes efficiently initiate to gather into a large plectonemic loop. Finally, Hi-C analysis shows links chromosomal regions containing positive supercoiling cis. Altogether, our findings indicate controls three-dimensional organization recognizing initiating DNA.

Language: Английский

Citations

30

Sequence-dependent activity and compartmentalization of foreign DNA in a eukaryotic nucleus DOI
Léa Meneu, Christophe Chapard, Jacques Serizay

et al.

Science, Journal Year: 2025, Volume and Issue: 387(6734)

Published: Feb. 6, 2025

In eukaryotes, DNA-associated protein complexes coevolve with genomic sequences to orchestrate chromatin folding. We investigate the relationship between DNA sequence and spontaneous loading activity of components in absence coevolution. Using bacterial genomes integrated into Saccharomyces cerevisiae , which diverged from yeast more than 2 billion years ago, we show that nucleosomes, cohesins, associated transcriptional machinery can lead formation two different archetypes, one transcribed other silent, independently heterochromatin formation. These archetypes also form on eukaryotic exogenous sequences, depend composition, be predicted using neural networks trained native genome. They do not mix nucleus, leading a bipartite nuclear compartmentalization, reminiscent organization vertebrate nuclei.

Language: Английский

Citations

2

A cohesin traffic pattern genetically linked to gene regulation DOI
Anne-Laure Valton, Sergey V. Venev, Barbara Mair

et al.

Nature Structural & Molecular Biology, Journal Year: 2022, Volume and Issue: 29(12), P. 1239 - 1251

Published: Dec. 1, 2022

Language: Английский

Citations

60

Enhancer-gene specificity in development and disease DOI Open Access
Tomás Pachano, Endika Haro, Álvaro Rada-Iglesias

et al.

Development, Journal Year: 2022, Volume and Issue: 149(11)

Published: June 1, 2022

ABSTRACT Enhancers control the establishment of spatiotemporal gene expression patterns throughout development. Over past decade, development new technologies has improved our capacity to link enhancers with their target genes based on colocalization within same topological domains. However, mechanisms that regulate how specifically activate some but not others a given domain remain unclear. In this Review, we discuss recent insights into factors controlling enhancer specificity, including genetic composition and promoters, linear 3D distance between genes, cell-type specific chromatin landscapes. We also elucidating molecular principles specificity might help us better understand predict pathological consequences human genetic, epigenetic structural variants.

Language: Английский

Citations

43