[PDF][PDF] eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci

K Mousavi, H Zare, S Dell'Orso, L Grontved… - Molecular cell, 2013 - cell.com
K Mousavi, H Zare, S Dell'Orso, L Grontved, G Gutierrez-Cruz, A Derfoul, GL Hager…
Molecular cell, 2013cell.com
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 (ie, 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 …
Summary
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 CERNA enhanced RNA polymerase II (Pol II) occupancy and transcription at MYOD1, DRRRNA 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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