MyoD induced enhancer RNA interacts with hnRNPL protein via CAAA motif to activate target gene transcription during myogenic differentiation
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AbstractEmerging evidence supports active roles of enhancer RNAs (eRNAs) in regulating target gene expression but our understanding of the underlying mechanisms remains incomplete. Here, we study eRNA regulation and function using skeletal myoblast differentiation as a paradigm. We provide a panoramic view of enhancer transcription and dynamics during myogenic differentiation and first categorization of eRNAs by integrating GRO-seq and RNA-seq data. We demonstrate the essential role of master transcription factor MyoD in activating eRNA production. Subsequent in depth dissection of super enhancer (se) generated seRNA-1 and -2 uncovered that seRNAs can promote myogenic differentiation in vitro and in vivo. Mechanistically, we found these seRNAs control the transcription of target genes by specifically binding to heterogeneous nuclear ribonucleoprotein L (hnRNPL) and modulate hnRNPL dosage on the target promoter. A CAAA tract on seRNA-1 was further identified to be essential in mediating seRNA-1/hnRNPL binding and function. Disruption of seRNA-hnRNPL interaction attenuates Pol II and H3K36me3 deposition at the target genes, in coincidence with the reduction of their transcription. Furthermore, analyses of hnRNPL binding transcriptome-wide reveal its association with eRNAs is a general phenomenon in multiple cells. Collectively, we propose that eRNA-hnRNPL interaction represents a novel mechanism contributing to target mRNA activation.
All Author(s) ListYu Zhao, Jiajian Zhou, Liangqiang He, Yuying Li, Jie Yuan, Kun Sun, Xiaona Chen, Xichen Bao, Miguel A. Esteban, Hao Sun, Huating Wang
Name of ConferenceInternational Human Epigenome Consortium Annual Meeting 2018
Start Date of Conference26/10/2018
End Date of Conference28/10/2018
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Year2018
LanguagesEnglish-United States

Last updated on 2019-10-06 at 14:16