Journal
NATURE GENETICS
Volume 51, Issue 9, Pages 1369-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-019-0485-9
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Funding
- JSPS [16H06153, 18H03992, 16H02902]
- Kanae Foundation for the Promotion of Medical Science
- Ono Medical Research Foundation
- Takeda Science Foundation
- Japan Foundation for Applied Enzymology
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- AMED [18ek0109282h0002]
- RIKEN Junior Research Associate Program
- International Program Associate program
- Karolinska Institutet
- Invitational Fellowships for Research in Japan [F1606103]
- Knut and Alice Wallenberg Foundation (Sweden)
- Royal Society Wolfson Research Merit Award (UK)
- Grants-in-Aid for Scientific Research [18H03992, 16H06153, 16H02902] Funding Source: KAKEN
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Promoters and enhancers are key cis-regulatory elements, but how they operate to generate cell type-specific transcriptomes is not fully understood. We developed a simple and robust method, native elongating transcript-cap analysis of gene expression (NET-CAGE), to sensitively detect 5' ends of nascent RNAs in diverse cells and tissues, including unstable transcripts such as enhancer-derived RNAs. We studied RNA synthesis and degradation at the transcription start site level, characterizing the impact of differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without the influence of RNA turnover, and show that enhancer-promoter pairs are generally activated simultaneously on stimulation. By integrating NET-CAGE data with chromatin interaction maps, we show that cis-regulatory elements are topologically connected according to their cell type specificity. We identified new enhancers with high sensitivity, and delineated primary locations of transcription within super-enhancers. Our NET-CAGE dataset derived from human and mouse cells expands the FANTOM5 atlas of transcribed enhancers, with broad applicability to biomedical research.
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