title: eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci.
abstract: Transcription factors and DNA regulatory binding motifs are fundamental components of the gene regulatory network. Here, by using genome-wide binding profiling, we show extensive occupancy of transcription factors of myogenesis (MyoD and Myogenin) at extragenic enhancer regions coinciding with RNA synthesis (i.e., eRNA). In particular, multiple regions were transcribed to eRNA within the regulatory region of MYOD1, including previously characterized distal regulatory regions (DRR) and core enhancer (CE). While (CE)RNA enhanced RNA polymerase II (Pol II) occupancy and transcription at MYOD1, (DRR)RNA acted to activate the downstream myogenic genes. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding Pol II assembly. By nuclease sensitivity assay, we found that eRNAs regulate genomic access of the transcriptional complex to defined regulatory regions. In conclusion, our data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events.
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA. Electronic address: kambizmousavi@gmail.com.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Mousavi
authors.forename: Hossein
authors.initials: H
authors.lastname: Zare
authors.forename: Stefania
authors.initials: S
authors.lastname: Dell'orso
authors.forename: Lars
authors.initials: L
authors.lastname: Grontved
authors.forename: Gustavo
authors.initials: G
authors.lastname: Gutierrez-Cruz
authors.forename: Assia
authors.initials: A
authors.lastname: Derfoul
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Hager
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051379:Mice; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D012313:RNA; D012319:RNA Polymerase II