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 Bioljournal_title
ACS chemical biologyauthors
Zhao C,Zhang Y,Zhao Y,Ying Y,Ai R,Zhang J,Wang Ydoi
10.1021/acschembio.7b00606subject
Has Abstractpub_date
2018-03-16 00:00:00pages
609-617issue
3eissn
1554-8929issn
1554-8937journal_volume
13pub_type
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