title: Dynamic estrogen receptor interactomes control estrogen-responsive trefoil Factor (TFF) locus cell-specific activities.
abstract: Estradiol signaling is ideally suited for analyzing the molecular and functional linkages between the different layers of information directing transcriptional regulations: the DNA sequence, chromatin modifications, and the spatial organization of the genome. Hence, the 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 regulation of colinear genes, identifying which ER binding sites (ERBSs) regulate a given gene still remains a challenge. Here, we investigated the coordination of such regulatory events at a 2-Mb genomic locus containing the estrogen-sensitive trefoil factor (TFF) cluster of genes in breast cancer cells. We demonstrate 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 provide evidence of a formerly suggested cooperation of enhancers toward gene regulation and also show that redundancy between ERBSs can occur.
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Quintin
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Le Péron
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Palierne
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Bizot
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cunha
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Aurélien A
authors.initials: AA
authors.lastname: Sérandour
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Avner
authors.affiliation: Cytogenetics and Cellular Biology Department, CHU, Rennes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Henry
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Percevault
authors.affiliation: Cytogenetics and Cellular Biology Department, CHU, Rennes, France BIOSIT, UMR CNRS 6290, Université de Rennes I, Faculté de Médecine, Rennes, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Belaud-Rotureau
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Huet
authors.affiliation: Equipe CC, UMR CNRS 6290, Université de Rennes I, Faculté de Médecine, Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Watrin
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France INSERM U1011, Université Lille-Nord de France, Faculté de Médecine de Lille-Pôle Recherche, Lille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Eeckhoute
authors.affiliation: Equipe EGD, UMR CNRS 6290, Université de Rennes I, Faculté de Médecine, Rennes, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Legagneux
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Salbert
authors.affiliation: Equipe SP@RTE, UMR CNRS 6290, Equipe Labellisée Ligue contre le Cancer, Université de Rennes I, Rennes, France raphael.metivier@univ-rennes1.fr.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Métivier
mesh_terms: D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D061986:MCF-7 Cells; D060885:Multiplex Polymerase Chain Reaction; D009687:Nuclear Proteins / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*; D000071164:Trefoil Factor-2; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004967:Estrogens; D009687:Nuclear Proteins; D009841:Oligonucleotides; D010455:Peptides; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D000071164:Trefoil Factor-2; D000097722:Cohesins; C000619697:CTCF protein, human; C429022:RAD21 protein, human
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