The power of proximity: mechanisms and biological roles of transvection DOI Creative Commons
Benjamin Prud’homme

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 89, P. 102269 - 102269

Published: Oct. 4, 2024

The phenomenon of transvection, defined as a proximity-dependent interallelic interaction, has been observed in the context complementation between mutant alleles for numerous Drosophila genes. Cases transvection-like phenomena have also other species, including mammals. However, potential contribution transvection to wild-type gene regulation and underlying mechanisms remain uncertain. Here, I review recent evidence demonstrating relevance physiological contexts. These findings suggest that represents an additional layer allows cells fine-tune expression based on proximity homologous alleles. In addition, studies measured physical distance interacting alleles, revealing unexpectedly large variable distances. will discuss how these distances are compatible with 'hub' model transcriptional regulation.

Language: Английский

Chromosome structure in Drosophila is determined by boundary pairing not loop extrusion DOI Creative Commons
Xinyang Bing, Wenfan Ke, Miki Fujioka

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 5, 2024

Two different models have been proposed to explain how the endpoints of chromatin looped domains (‘TADs’) in eukaryotic chromosomes are determined. In first, a cohesin complex extrudes loop until it encounters boundary element roadblock, generating stem-loop. this model, boundaries functionally autonomous: they an intrinsic ability halt movement incoming complexes that is independent properties neighboring boundaries. second, loops generated by boundary:boundary pairing. non-autonomous, and their form depends upon well match with neighbors. Moreover, unlike loop-extrusion pairing interactions can generate both stem-loops circle-loops. We used combination MicroC analyze TADs organized, experimental manipulations even skipped TAD boundary, homie , test predictions ‘loop-extrusion’ ‘boundary-pairing’ models. Our findings incompatible instead suggest flies determined mechanism which elements physically pair partners, either head-to-head or head-to-tail, varying degrees specificity. Although our experiments do not address partners find each other, unlikely require extrusion.

Language: Английский

Citations

9
An extrinsic motor directs chromatin loop formation by cohesin DOI Creative Commons
Thomas M Guérin, Christopher Barrington, Georgii Pobegalov

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(19), P. 4173 - 4196

Published: Aug. 19, 2024

Language: Английский

Citations

9
Stem-loop and circle-loop TADs generated by directional pairing of boundary elements have distinct physical and regulatory properties DOI Creative Commons
Wenfan Ke, Miki Fujioka, Paul Schedl

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 5, 2024

The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing typically orientation-dependent. Pairing can be head-to-tail or head-to-head. former generates stem-loop TAD, while the latter gives circle-loop TAD. TAD that encompasses Drosophila even skipped ( eve ) gene is nhomie homie To explore relationship loop topology regulatory landscape, we flanked boundary region with two attP sites. sites were then used to generate four replacements: λ DNA , forward (WT orientation), reverse (opposite WT (same orientation as ). replacement restores landscape: MicroC experiments, ‘volcano’ triangle topped plume, its elements sequestered from neighbors. lacks function: endpoint ‘new’ on side ill-defined, stripe enhancers activate nearby gene, eIF3j . While restore circle-loop, this changes local landscape. interacts neighbors, plume at top peak converted pair ‘clouds’ contacts next-door Consistent loss isolation afforded topology, weakly genes Conversely, function partially disrupted.

Language: Английский

Citations

5
A unified model for cohesin function in sisterchromatid cohesion and chromatin loop formation DOI Creative Commons
Frank Uhlmann

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(6), P. 1058 - 1071

Published: March 1, 2025

The ring-shaped cohesin complex topologically entraps two DNAs to establish sister chromatid cohesion. Cohesin also shapes the interphase chromatin landscape by forming DNA loops, which it is thought achieve using an in vitro-observed loop extrusion mechanism. However, recent studies revealed that loop-extrusion-deficient retains its ability form suggesting a divergence of vitro and vivo formation. Instead extrusion, we examine whether forms loops mechanism akin cohesion establishment: sequential topological capture DNAs. We explore similarities differences between "loop capture" extrusion" model, how they compare at explaining experimental observations, future approaches can delineate their possible respective contributions. extend our DNA-DNA model for function related structural maintenance chromosomes (SMC) family members, condensin, Smc5-Smc6 complex, bacterial SMC complexes.

Language: Английский

Citations

0
Principles of long-range gene regulation DOI Creative Commons
Sanyami Zunjarrao, Maria Cristina Gambetta

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 91, P. 102323 - 102323

Published: Feb. 13, 2025

Transcription from gene promoters occurs in specific spatiotemporal patterns multicellular organisms, controlled by genomic regulatory elements. The communication between a element and promoter requires certain degree of physical proximity them; hence, most regulation locally the genome. However, recent discoveries have revealed long-range strategies that enhance interactions elements overcoming distances them linear These new findings challenge traditional view how expression are controlled. This review examines recently reported Drosophila mammals, offering insights into their mechanisms evolution.

Language: Английский

Citations

0
Chromatin domains in the cell: Phase separation and condensation DOI
Shin Fujishiro, Masaki Sasai, Kazuhiro Maeshima

et al.

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 91, P. 103006 - 103006

Published: Feb. 20, 2025

Language: Английский

Citations

0
Stem-loop and circle-loop TADs generated by directional pairing of boundary elements have distinct physical and regulatory properties DOI Creative Commons
Wenfan Ke, Miki Fujioka, Paul Schedl

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 7, 2024

The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing typically orientation-dependent. Pairing can be head-to-tail or head-to-head. former generates stem-loop TAD, while the latter gives circle-loop TAD. TAD that encompasses Drosophila even skipped ( eve ) gene is nhomie homie To explore relationship loop topology regulatory landscape, we flanked boundary region with two attP sites. sites were then used to generate four replacements: λ DNA , forward (WT orientation), reverse (opposite WT (same orientation as ). replacement restores landscape: MicroC experiments, ‘volcano’ triangle topped plume, its elements sequestered from neighbors. lacks function: endpoint ‘new’ on side ill-defined, stripe enhancers activate nearby gene, eIF3j . While restore circle-loop, this changes local landscape. interacts neighbors, plume at top peak converted pair ‘clouds’ contacts next-door Consistent loss isolation afforded topology, weakly genes Conversely, function partially disrupted.

Language: Английский

Citations

3
Deciphering the 3D genome organization across species from Hi-C data DOI Creative Commons

Aleksei Shkolikov,

Aleksandra A. Galitsyna, Mikhail S. Gelfand

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Abstract Three-dimensional (3D) genome organization plays a critical role in gene expression regulation and function. Recent advances Hi-C Micro-C data across various species provide insights into the mechanisms governing 3D formation, such as loop extrusion. While visual patterns like topologically associating domains (TADs) loops are conserved species, underlying biological may differ. Both species-specific architectural factors DNA sequences influence chromatin folding, complicating comparative studies on evolution of genome. This work leverages existing machine learning to explore folding predict structures from sequences. Here, we present Chimaera (convolutional neural network for maps prediction using autoencoder representation), that not only predicts sequence, but also enables search, quantification, interpretation associations between patterns. Firstly, demonstrate or contact sequences, enabling extraction key mechanisms. By exploring latent representations generated by Chimaera, offer tool building an unsupervised atlas features insulation, loops, stripes, fountains/jets. We capabilities detecting quantifying signatures insulation fountains data, applying it well-characterized processes cell cycle embryogenesis. Additionally, perform targeted search sequence elements associated with specific structures, advancing our understanding organization. extending multiple confirm CTCF generating vertebrates BEAF-32 Drosophila , identify motifs previously reported mouse . In Dictyostelium demonstrates importance arrangement strand formation confirming hypothesis about impact convergent positioning this amoeba. A pronounced diverse effect genes is evident when predicting interactions other organisms. Finally, train model one then apply cross-predict how genomes organisms might fold within cellular environment original species. thereby test whether transferable reveal evolutionary similarities chromatin-based cluster tree ranging plants mammals. Key takeaways genomic interaction Chimaera’s unique architecture integrates encoder, allowing recurring their offers unified metric 3D-genome features, exploration validation complex hypotheses regarding principles including sequence-specific at protein binding sites genes. tasks biology demonstrating its ability consequences rearrangements, mutations, insertions.

Language: Английский

Citations

0
The power of proximity: mechanisms and biological roles of transvection DOI Creative Commons
Benjamin Prud’homme

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 89, P. 102269 - 102269

Published: Oct. 4, 2024

The phenomenon of transvection, defined as a proximity-dependent interallelic interaction, has been observed in the context complementation between mutant alleles for numerous Drosophila genes. Cases transvection-like phenomena have also other species, including mammals. However, potential contribution transvection to wild-type gene regulation and underlying mechanisms remain uncertain. Here, I review recent evidence demonstrating relevance physiological contexts. These findings suggest that represents an additional layer allows cells fine-tune expression based on proximity homologous alleles. In addition, studies measured physical distance interacting alleles, revealing unexpectedly large variable distances. will discuss how these distances are compatible with 'hub' model transcriptional regulation.

Language: Английский

Citations

0