2019年度 医学研セミナー

Dynamics and Topology of Human Transcribed Cis-regulatory Elements

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演者 村川 泰裕 Ph.D.
理化学研究所 生命医科学研究センター (チームリーダー)
会場 東京都医学総合研究所 2階講堂
日時 2019年7月29日(月) 14:30〜15:30
世話人 所長 正井 久雄
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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 the influence of RNA turnover, and revealed that enhancer-promoter pairs are generally activated simultaneously upon cellular stimulation. By integrating NET-CAGE data with chromatin interaction maps, we showed 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.