RT Journal Article
SR Electronic
T1 Inducible, tunable and multiplex human gene regulation using CRISPR-Cpf1-based transcription factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 150656
DO 10.1101/150656
A1 Yu Gyoung Tak
A1 Benjamin P. Kleinstiver
A1 James K. Nuñez
A1 Jonathan Y. Hsu
A1 Jingyi Gong
A1 Jonathan S. Weissman
A1 J. Keith Joung
YR 2017
UL http://biorxiv.org/content/early/2017/06/15/150656.abstract
AB Targeted and inducible regulation of mammalian gene expression is a broadly important research capability that may also enable development of novel therapeutics for treating human diseases. Here we demonstrate that a catalytically inactive RNA-guided CRISPR-Cpf1 nuclease fused to transcriptional activation domains can up-regulate endogenous human gene expression. We engineered drug-inducible Cpf1-based activators and show how this system can be used to tune the regulation of endogenous gene transcription in human cells. Leveraging the simpler multiplex capability of the Cpf1 platform, we show that we can induce both synergistic and combinatorial gene expression in human cells. Our work should enable the creation of other Cpf1-based gene regulatory fusion proteins and the development of multiplex gene perturbation library screens for understanding complex cellular phenotypes.