Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics.

Date publication

décembre 2024

Journal

Science advances

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MOLINA Nacho , Dr SEXTON Thomas

Tous les auteurs :
Platania A, Erb C, Barbieri M, Molcrette B, Grandgirard E, de Kort MAC, Pomp W, Meaburn K, Taylor T, Shchuka VM, Kocanova S, Nazarova M, Oliveira GM, Mitchell JA, Soutoglou E, Lenstra TL, Molina N, Papantonis A, Bystricky K, Sexton T

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39671497

Résumé

The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding is lacking. We combine simultaneous live tracking of pairs of genomic loci and nascent transcripts with molecular dynamics simulations to assess the gene and its enhancer. We find that both loci exhibit more constrained mobility than control sequences due to stalled cohesin at CCCTC-binding factor sites. Strikingly, enhancer mobility becomes constrained on transcriptional firing, homogenizing its dynamics with the gene promoter, suggestive of their cotranscriptional sharing of a nuclear microenvironment. Furthermore, we find transcription and loop extrusion to be antagonistic processes constraining regulatory loci. These findings indicate that modulating chromatin mobility can be an additional, underestimated means for effective gene regulation.

Mots clés

Enhancer Elements, Genetic, Promoter Regions, Genetic, Transcription, Genetic, Chromatin, genetics, Cohesins, SOXB1 Transcription Factors, genetics, Humans, Gene Expression Regulation, Molecular Dynamics Simulation, Cell Cycle Proteins, genetics, Chromosomal Proteins, Non-Histone, genetics, CCCTC-Binding Factor, metabolism

Référence

Sci Adv. 2024 12 13;10(50):eadq0987