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bioRxiv · 10.1101/689968

Dynamics and Topology of Human Transcribed Cis-regulatory Elements

Hirabayashi, S.·Bhagat, S.·Matsuki, Y.·Takegami, Y.·Uehata, T.·Kanemaru, A.·Itoh, M.·Shirakawa, K.·Takaori-Kondo, A.·Takeuchi, O.·Carninci, P.·Katayama, S.·Hayashizaki, Y.·Kere, J.·Kawaji, H.·Murakawa, Y.
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Abstract

Promoters and enhancers are key cis-regulatory elements, but how they orchestrate to generate cell-type-specific transcriptomes remains elusive. We developed a simple and robust approach to globally determine 5-ends of nascent RNAs (NET-CAGE) in diverse cells and tissues, thereby sensitively detecting unstable transcripts including enhancer-derived RNAs. We studied RNA synthesis and degradation at the transcription start site level, uncovering the impact of differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without influence of RNA turnover, and identified enhancer-promoter pairs which were simultaneously activated upon cellular stimulation. By integrating NET-CAGE data with chromatin interaction maps, we revealed that cis-regulatory elements are topologically connected according to their cell-type specificity. We discovered new enhancers with high sensitivity, and delineated primary locations of transcription within super-enhancers. Our collection of NET-CAGE data from human and mouse significantly expanded the FANTOM5 catalogue of transcribed enhancers, with broad applicability to biomedical research. (148 words)

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Hirabayashi, S., Bhagat, S., Matsuki, Y., Takegami, Y., Uehata, T., Kanemaru, A., Itoh, M., Shirakawa, K., Takaori-Kondo, A., Takeuchi, O., Carninci, P., Katayama, S., Hayashizaki, Y., Kere, J., Kawaji, H., Murakawa, Y.. 2019-07-03. Dynamics and Topology of Human Transcribed Cis-regulatory Elements. https://doi.org/10.1101/689968

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