Dynamic ER Interactomes Control the Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities.

Justine Quintin (1) , Christine Le Péron (2) , Gaëlle Palierne (2) , Maud Bizot (2) , Stéphanie Cunha (1) , Aurélien A Sérandour (1, 3) , Stéphane Avner (2) , Catherine Henry (4) , Frédéric Percevault (5) , Marc-Antoine Belaud-Rotureau (2, 4) , Sébastien Huet (2, 6) , Erwan Watrin (2) , Jérôme Eeckhoute (7) , Vincent Legagneux (8) , Gilles Salbert (2) , Raphaël Métivier (2)

1 ICM - Interactions cellulaires et moléculaires
2 IGDR - Institut de Génétique et Développement de Rennes
3 Cancer Research UK Cambridge Institute
4 Service de Cytogénétique et de Biologie Cellulaire
5 Irset - Institut de recherche en santé, environnement et travail
6 EMBL - European Molecular Biology Laboratory [Heidelberg]
7 RNMCD - Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011
8 IGDR - Institut de Génétique et Développement de Rennes

: Estradiol signaling is ideally suited for analyzing molecular and functional linkages between the different layers of information directing transcriptional regulations: DNA sequence, chromatin modifications and the spatial organization of the genome. Hence, estrogen receptor (ER) can bind at a distance from its target genes and engages timely and spatially coordinated processes to regulate their expression. In the context of the coordinated regulations of co-linear genes, identifying which ER binding sites (ERBSs) regulate a given gene still remains a challenging question. Here, we investigated the coordination of such regulatory events at a 2 Mb genomic locus containing the estrogen-sensitive TFF cluster of genes in breast cancer cells. We demonstrated that this locus exhibits a hormone and cohesin-dependent reduction in the plasticity of its three-dimensional organization that allows multiple ERBSs to be dynamically brought to the vicinity of estrogen-sensitive genes. Additionally, by using triplex forming oligonucleotides, we could precisely document the functional links between ER engagement at given ERBSs and the regulation of particular genes. Hence, our data evidence a formerly suggested cooperation of enhancers towards gene regulations, and also show that redundancy between ERBSs can occur.

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular biology

Justine Quintin, Christine Le Péron, Gaëlle Palierne, Maud Bizot, Stéphanie Cunha, et al.. Dynamic ER Interactomes Control the Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities.. Molecular and Cellular Biology, 2014, 34 (13), pp.2418-2436. ⟨10.1128/MCB.00918-13⟩. ⟨hal-00984591⟩