title: Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells.
abstract: Estrogen receptor (ER) binds to distal enhancers within the genome and requires additional factors, such as the Forkhead protein FoxA1, for mediating chromatin interactions. We now show that the human Groucho protein, Transducin-like enhancer protein 1 (TLE1), positively assists some ER-chromatin interactions, a role that is distinct from its general role as a transcriptional repressor. We show that specific silencing of TLE1 inhibits the ability of ER to bind to a subset of ER binding sites within the genome, a phenomenon that results in perturbations in phospho-RNA Pol II recruitment. Furthermore, TLE1 is essential for effective ER-mediated cell division. We have discovered a distinct role for TLE1, as a necessary transcriptional component of the ER complex, where it facilitates ER-chromatin interactions.
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Holmes
authors.forename: Antoni
authors.initials: A
authors.lastname: Hurtado
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Rosalind
authors.initials: R
authors.lastname: Launchbury
authors.forename: Caryn S
authors.initials: CS
authors.lastname: Ross-Innes
authors.forename: James
authors.initials: J
authors.lastname: Hadfield
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Odom
authors.forename: Jason S
authors.initials: JS
authors.lastname: Carroll
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002843:Chromatin; D056970:Co-Repressor Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D012097:Repressor Proteins; C499043:TLE1 protein, human