多路复用
增强子
Wnt信号通路
基因组
调节顺序
计算生物学
生物
基因
基因表达调控
遗传学
基因表达
作者
Wei Chen,Junhong Choi,Xiaoyi Li,Jenny F. Nathans,Beth Martin,Wei Yang,Nobuhiko Hamazaki,Chengxiang Qiu,Jean‐Benoît Lalanne,Samuel G. Regalado,Haedong Kim,Vikram Agarwal,Eva K. Nichols,Anh Leith,Choli Lee,Jay Shendure
出处
期刊:Nature
[Springer Nature]
日期:2024-07-17
被引量:1
标识
DOI:10.1038/s41586-024-07706-4
摘要
Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit. We show how this strategy can be used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility. Leveraging signal transduction pathway-responsive cis-regulatory elements, we also demonstrate time- and concentration-dependent genomic recording of WNT, NF-κB and Tet-On activities. By coupling ENGRAM to sequential genome editing via DNA Typewriter
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