title: Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation.
abstract: The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17β-oestradiol (E2)-bound oestrogen receptor α (ER-α) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer-promoter looping initiated by ER-α binding. Cohesin, present on many ER-α-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-α/eRNA-induced enhancer-promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Li
authors.forename: Dimple
authors.initials: D
authors.lastname: Notani
authors.forename: Qi
authors.initials: Q
authors.lastname: Ma
authors.forename: Bogdan
authors.initials: B
authors.lastname: Tanasa
authors.forename: Esperanza
authors.initials: E
authors.lastname: Nunez
authors.forename: Aaron Yun
authors.initials: AY
authors.lastname: Chen
authors.forename: Daria
authors.initials: D
authors.lastname: Merkurjev
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ohgi
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Song
authors.forename: Soohwan
authors.initials: S
authors.lastname: Oh
authors.forename: Hong-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects* / Q000235:genetics; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004958:Estradiol; D047628:Estrogen Receptor alpha; D004967:Estrogens; D008024:Ligands; D022661:RNA, Untranslated; D000097722:Cohesins; C506487:ESR1 protein, human