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

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftMolecular Cell
Vol/bind51
Udgave nummer5
Sider (fra-til)606-17
ISSN1097-2765
DOI
StatusUdgivet - 2013

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Mousavi, K., Zare, H., Dell'orso, S., Grøntved, L., Gutierrez-Cruz, G., Derfoul, A., Hager, G. L., & 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