5 June 2024 | Dig B. Mahat, Nathaniel D. Tippens, Jorge D. Martin-Rufino, Sean K. Waterton, Jiayu Fu, Sarah E. Blatt & Phillip A. Sharp
This study introduces scGRO-seq, a novel single-cell nascent RNA sequencing method that uses click chemistry to measure gene and enhancer activity in individual cells. The method provides a comprehensive view of the dynamic nature of transcription, revealing 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 and can elucidate cell cycle dynamics using replication-dependent non-polyadenylated histone gene transcription. The single-nucleotide spatial and temporal resolution of scGRO-seq enables the identification of networks of enhancers and genes, suggesting that transcription initiation at super-enhancers precedes activation in associated genes. The study demonstrates the ability of scGRO-seq to investigate transcription regulation mechanisms and the role of enhancers in gene expression, offering insights into the dynamic nature of global transcription and the origin and propagation of transcription signals.This study introduces scGRO-seq, a novel single-cell nascent RNA sequencing method that uses click chemistry to measure gene and enhancer activity in individual cells. The method provides a comprehensive view of the dynamic nature of transcription, revealing 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 and can elucidate cell cycle dynamics using replication-dependent non-polyadenylated histone gene transcription. The single-nucleotide spatial and temporal resolution of scGRO-seq enables the identification of networks of enhancers and genes, suggesting that transcription initiation at super-enhancers precedes activation in associated genes. The study demonstrates the ability of scGRO-seq to investigate transcription regulation mechanisms and the role of enhancers in gene expression, offering insights into the dynamic nature of global transcription and the origin and propagation of transcription signals.