Competition between transcription and loop extrusion modulates promoter and enhancer dynamics - Archive ouverte HAL Access content directly
Preprints, Working Papers, ... Year : 2023

Competition between transcription and loop extrusion modulates promoter and enhancer dynamics

Mariano Barbieri
  • Function : Author
Marit Ac de Kort
  • Function : Author
Karen Meaburn
  • Function : Author
Tiegh Taylor
  • Function : Author
Virlana M Shchuka
  • Function : Author
Jennifer A Mitchell
Evi Soutoglou
  • Function : Author
Tineke L Lenstra
  • Function : Author

Abstract

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.
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Dates and versions

hal-04312310 , version 1 (28-11-2023)

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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⟩
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