Multiple Chemical Inducible Tal Effectors for Genome Editing and Transcription Activation.

Abstract:

:Inducible modulation is often required for precise investigations and manipulations of dynamic biological processes. Transcription activator-like effectors (TALEs) provide a powerful tool for targeted gene editing and transcriptional programming. We designed a series of chemical inducible systems by coupling TALEs with a mutated human estrogen receptor (ERT2), which renders them 4-hydroxyl-tamoxifen (4-OHT) inducible for access of the genome. Chemical inducible genome editing was achieved via fusing two tandem ERT2 domains to customized transcription activator-like effector nuclease (TALEN), which we termed "Hybrid Inducible Technology" (HIT-TALEN). Those for transcription activation were vigorously optimized using multiple construct designs. Most efficient drug induction for endogenous gene activation was accomplished with minimal background activity using an optimized inducible TALE based SunTag system (HIT-TALE-SunTag). The HIT-SunTag system is rapid, tunable, selective to 4-OHT over an endogenous ligand, and reversible in drug induced transcriptional activation. Versatile systems developed in this study can be easily applied for editing and transcriptional programming of potentially any genomic loci in a tight and effective chemical inducible fashion.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Zhao C,Zhang Y,Zhao Y,Ying Y,Ai R,Zhang J,Wang Y

doi

10.1021/acschembio.7b00606

subject

Has Abstract

pub_date

2018-03-16 00:00:00

pages

609-617

issue

3

eissn

1554-8929

issn

1554-8937

journal_volume

13

pub_type

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