Single-cell nascent RNA sequencing unveils coordinated global transcription.

Autor: Mahat DB; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Tippens ND; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Martin-Rufino JD; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Waterton SK; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Stanford University, Stanford, CA, USA., Fu J; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL, USA., Blatt SE; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Exact Sciences, Madison, WI, USA., Sharp PA; Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. sharppa@mit.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Jul; Vol. 631 (8019), pp. 216-223. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1038/s41586-024-07517-7
Abstrakt: Transcription is the primary regulatory step in gene expression. Divergent transcription initiation from promoters and enhancers produces stable RNAs from genes and unstable RNAs from enhancers 1,2 . Nascent RNA capture and sequencing assays simultaneously measure gene and enhancer activity in cell populations 3 . However, fundamental questions about the temporal regulation of transcription and enhancer-gene coordination remain unanswered, primarily because of the absence of a single-cell perspective on active transcription. In this study, we present scGRO-seq-a new single-cell nascent RNA sequencing assay that uses click chemistry-and unveil coordinated transcription throughout the genome. We demonstrate the episodic nature of transcription and the co-transcription of functionally related genes. scGRO-seq can estimate burst size and frequency by directly quantifying transcribing RNA polymerases in individual cells and can leverage replication-dependent non-polyadenylated histone gene transcription to elucidate cell cycle dynamics. The single-nucleotide spatial and temporal resolution of scGRO-seq enables the identification of networks of enhancers and genes. Our results suggest that the bursting of transcription at super-enhancers precedes bursting from associated genes. By imparting insights into the dynamic nature of global transcription and the origin and propagation of transcription signals, we demonstrate the ability of scGRO-seq to investigate the mechanisms of transcription regulation and the role of enhancers in gene expression.
(© 2024. The Author(s).)
Databáze: MEDLINE
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