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NET-CAGE Characterizes the Dynamics and Topology of Human Transcribed Cis-regulatory Elements

ABSTRACT: 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 approach to sensitively detect 5’-ends of nascent RNAs (NET-CAGE) in diverse cells and tissues, including unstable transcripts such as enhancer-derived RNAs. We studied RNA synthesis and degradation at the transcription start site (TSS) 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 upon 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 catalogue of transcribed enhancers, with broad applicability to biomedical research.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE118075 | GEO | 2019/06/10

REPOSITORIES: GEO

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