Fiche publication
Date publication
décembre 2020
Journal
Molecular cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MOLINA Nacho
Tous les auteurs :
Sönmezer C, Kleinendorst R, Imanci D, Barzaghi G, Villacorta L, Schübeler D, Benes V, Molina N, Krebs AR
Lien Pubmed
Résumé
Gene activation requires the cooperative activity of multiple transcription factors at cis-regulatory elements (CREs). Yet, most transcription factors have short residence time, questioning the requirement of their physical co-occupancy on DNA to achieve cooperativity. Here, we present a DNA footprinting method that detects individual molecular interactions of transcription factors and nucleosomes with DNA in vivo. We apply this strategy to quantify the simultaneous binding of multiple transcription factors on single DNA molecules at mouse CREs. Analysis of the binary occupancy patterns at thousands of motif combinations reveals that high DNA co-occupancy occurs for most types of transcription factors, in the absence of direct physical interaction, at sites of competition with nucleosomes. Perturbation of pairwise interactions demonstrates the function of molecular co-occupancy in binding cooperativity. Our results reveal the interactions regulating CREs at molecular resolution and identify DNA co-occupancy as a widespread cooperativity mechanism used by transcription factors to remodel chromatin.
Mots clés
chromatin, enhancers, gene regulation, genomics, transcription factor cooperativity
Référence
Mol Cell. 2020 Dec 1;:
