Competition between transcription and loop extrusion modulates promoter and enhancer dynamics

Angeliki Platania (1) , Cathie Erb (1) , Mariano Barbieri , Bastien Molcrette (1) , Erwan Grandgirard (1) , Marit Ac de Kort , Karen Meaburn , Tiegh Taylor , Virlana M Shchuka , Silvia Kocanova (2) , Guilherme Monteiro Oliveira (1) , Jennifer A Mitchell , Evi Soutoglou , Tineke L Lenstra , Nacho Molina (1) , Argyris Papantonis (3) , Kerstin Bystricky (4, 2) , Tom Sexton (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 MCD - Unité de biologie Moléculaire, Cellulaire et du Développement
3 Institute of Pathology - University Medical Centre Göttingen
4 IUF - Institut universitaire de France

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 4D arrangement of the Sox2 gene and its enhancer, in response to a battery of perturbations. We find that alterations in chromatin mobility, not promoter-enhancer distance, is more informative about 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.

Domaines: Sciences du Vivant [q-bio]

Angeliki Platania, Cathie Erb, Mariano Barbieri, Bastien Molcrette, Erwan Grandgirard, et al.. Competition between transcription and loop extrusion modulates promoter and enhancer dynamics. 2023. ⟨hal-04312310⟩