biostudies-literatureLiang YNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)7329https://www.ebi.ac.uk/biostudies/studies/S-EPMC9705438biostudies-literatureUnknown13(1)Technologies for gene activation are valuable tools for the study of gene functions and have a wide range of potential applications in bioengineering and medicine. In contrast to existing methods based on recruiting transcriptional modulators via DNA-binding proteins, we developed a strategy termed Narta (nascent RNA-guided transcriptional activation) to achieve gene activation by recruiting artificial transcription factors (aTFs) to transcription sites through nascent RNAs of the target gene. Using Narta, we demonstrate robust activation of a broad range of exogenous and endogenous genes in various cell types, including zebrafish embryos, mouse and human cells. Importantly, the activation is reversible, tunable and specific. Moreover, Narta provides better activation potency of some expreNature communicationsGene activation guided by nascent RNA-bound transcription factors.PMC970543832171444Yin YXu PLiang YHuang HFu YXu HZhou YWang JChen BCheng TQian WQian PZou WfalseGene activation guided by nascent RNA-bound transcription factors.Technologies for gene activation are valuable tools for the study of gene functions and have a wide range of potential applications in bioengineering and medicine. In contrast to existing methods based on recruiting transcriptional modulators via DNA-binding proteins, we developed a strategy termed Narta (nascent RNA-guided transcriptional activation) to achieve gene activation by recruiting artificial transcription factors (aTFs) to transcription sites through nascent RNAs of the target gene. Using Narta, we demonstrate robust activation of a broad range of exogenous and endogenous genes in various cell types, including zebrafish embryos, mouse and human cells. Importantly, the activation is reversible, tunable and specific. Moreover, Narta provides better activation potency of some expre2022-01-01T00:00:00Z2022 Nov2025-04-26T09:39:18.151Z2025-04-26T09:39:18.151ZS-EPMC97054383644336710.1038/s41467-022-35041-7