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Competition between transcription and loop extrusion modulates promoter and enhancer dynamics
The spatiotemporal configuration of genes with distal regulatory elements, and the impact of chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts with transcription is also largely unkno...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462181/ https://www.ncbi.nlm.nih.gov/pubmed/37645793 http://dx.doi.org/10.21203/rs.3.rs-3164817/v1 |
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author | Sexton, Tom Platania, Angeliki Erb, Cathie Barbieri, Mariano Molcrette, Bastien Grandgirard, Erwan de Kort, Marit Meabum, Karen Taylor, Tiegh Shchuka, Virlana Kocanova, Silvia Oliveira, Guilherme Mitchell, Jennifer Soutoglou, Evi Lenstra, Tineke Molina, Nacho Papantonis, Argyris Bystricky, Keratin |
author_facet | Sexton, Tom Platania, Angeliki Erb, Cathie Barbieri, Mariano Molcrette, Bastien Grandgirard, Erwan de Kort, Marit Meabum, Karen Taylor, Tiegh Shchuka, Virlana Kocanova, Silvia Oliveira, Guilherme Mitchell, Jennifer Soutoglou, Evi Lenstra, Tineke Molina, Nacho Papantonis, Argyris Bystricky, Keratin |
author_sort | Sexton, Tom |
collection | PubMed |
description | The spatiotemporal configuration of genes with distal regulatory elements, and the impact of chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts with transcription is also largely unknown. We combine live tracking of genomic loci and nascent transcripts with molecular dynamics simulations to assess the spatiotemporal arrangement of the Sox2 gene and its enhancer, in response to a battery of perturbations. We find a close link between chromatin mobility and transcriptional status: active elements display more constrained mobility, consistent with confinement within specialized nuclear sites, and alterations in enhancer mobility distinguish poised from transcribing alleles. Strikingly, we find that whereas loop extrusion and transcription factor-mediated clustering contribute to promoter-enhancer proximity, they have antagonistic effects on chromatin dynamics. This provides an experimental framework for the underappreciated role of chromatin dynamics in genome regulation. |
format | Online Article Text |
id | pubmed-10462181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-104621812023-08-29 Competition between transcription and loop extrusion modulates promoter and enhancer dynamics Sexton, Tom Platania, Angeliki Erb, Cathie Barbieri, Mariano Molcrette, Bastien Grandgirard, Erwan de Kort, Marit Meabum, Karen Taylor, Tiegh Shchuka, Virlana Kocanova, Silvia Oliveira, Guilherme Mitchell, Jennifer Soutoglou, Evi Lenstra, Tineke Molina, Nacho Papantonis, Argyris Bystricky, Keratin Res Sq Article The spatiotemporal configuration of genes with distal regulatory elements, and the impact of chromatin mobility on transcription, remain unclear. Loop extrusion is an attractive model for bringing genetic elements together, but how this functionally interacts with transcription is also largely unknown. We combine live tracking of genomic loci and nascent transcripts with molecular dynamics simulations to assess the spatiotemporal arrangement of the Sox2 gene and its enhancer, in response to a battery of perturbations. We find a close link between chromatin mobility and transcriptional status: active elements display more constrained mobility, consistent with confinement within specialized nuclear sites, and alterations in enhancer mobility distinguish poised from transcribing alleles. Strikingly, we find that whereas loop extrusion and transcription factor-mediated clustering contribute to promoter-enhancer proximity, they have antagonistic effects on chromatin dynamics. This provides an experimental framework for the underappreciated role of chromatin dynamics in genome regulation. American Journal Experts 2023-08-16 /pmc/articles/PMC10462181/ /pubmed/37645793 http://dx.doi.org/10.21203/rs.3.rs-3164817/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Sexton, Tom Platania, Angeliki Erb, Cathie Barbieri, Mariano Molcrette, Bastien Grandgirard, Erwan de Kort, Marit Meabum, Karen Taylor, Tiegh Shchuka, Virlana Kocanova, Silvia Oliveira, Guilherme Mitchell, Jennifer Soutoglou, Evi Lenstra, Tineke Molina, Nacho Papantonis, Argyris Bystricky, Keratin Competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
title | Competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
title_full | Competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
title_fullStr | Competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
title_full_unstemmed | Competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
title_short | Competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
title_sort | competition between transcription and loop extrusion modulates promoter and enhancer dynamics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462181/ https://www.ncbi.nlm.nih.gov/pubmed/37645793 http://dx.doi.org/10.21203/rs.3.rs-3164817/v1 |
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