eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci

Kambiz Mousavi, Hossein Zare, Stefania Dell'orso, Lars Grøntved, Gustavo Gutierrez-Cruz, Assia Derfoul, Gordon L Hager, Vittorio Sartorelli

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalMolecular Cell
Volume51
Issue number5
Pages (from-to)606-17
ISSN1097-2765
DOIs
Publication statusPublished - 2013

Fingerprint

Nucleic Acid Regulatory Sequences
RNA
Myogenin
Chromatin Assembly and Disassembly
Muscle Development
RNA Polymerase II
DNA

Keywords

  • Animals
  • Binding Sites
  • Cell Line
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Mice
  • MyoD Protein
  • Myogenin
  • Promoter Regions, Genetic
  • RNA
  • RNA Polymerase II

Cite this

Mousavi, K., Zare, H., Dell'orso, S., Grøntved, L., Gutierrez-Cruz, G., Derfoul, A., ... Sartorelli, V. (2013). eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. Molecular Cell, 51(5), 606-17. https://doi.org/10.1016/j.molcel.2013.07.022
Mousavi, Kambiz ; Zare, Hossein ; Dell'orso, Stefania ; Grøntved, Lars ; Gutierrez-Cruz, Gustavo ; Derfoul, Assia ; Hager, Gordon L ; Sartorelli, Vittorio. / eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. In: Molecular Cell. 2013 ; Vol. 51, No. 5. pp. 606-17.
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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.",
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Mousavi, K, Zare, H, Dell'orso, S, Grøntved, L, Gutierrez-Cruz, G, Derfoul, A, Hager, GL & Sartorelli, V 2013, 'eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci', Molecular Cell, vol. 51, no. 5, pp. 606-17. https://doi.org/10.1016/j.molcel.2013.07.022

eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. / Mousavi, Kambiz; Zare, Hossein; Dell'orso, Stefania; Grøntved, Lars; Gutierrez-Cruz, Gustavo; Derfoul, Assia; Hager, Gordon L; Sartorelli, Vittorio.

In: Molecular Cell, Vol. 51, No. 5, 2013, p. 606-17.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci

AU - Mousavi, Kambiz

AU - Zare, Hossein

AU - Dell'orso, Stefania

AU - Grøntved, Lars

AU - Gutierrez-Cruz, Gustavo

AU - Derfoul, Assia

AU - Hager, Gordon L

AU - Sartorelli, Vittorio

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Cell Line

KW - Chromatin

KW - Chromatin Assembly and Disassembly

KW - Enhancer Elements, Genetic

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Mice

KW - MyoD Protein

KW - Myogenin

KW - Promoter Regions, Genetic

KW - RNA

KW - RNA Polymerase II

U2 - 10.1016/j.molcel.2013.07.022

DO - 10.1016/j.molcel.2013.07.022

M3 - Journal article

C2 - 23993744

VL - 51

SP - 606

EP - 617

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 5

ER -