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Published on: May 7, 2018
DOCTER: a genetically encoded switchable protein module for ERα-mediated transcriptional regulation
Jinmin Wang1, Jingfang Liu1, Dandan Peng2
1Department of Biomedical Engineering, MOE Key Laboratory of Biomedical Engineering, Zhejiang Provincial Key Laboratory of Intelligent Sensing and Advanced Medical Instrument, Zhejiang University, Hangzhou, China.
None:
The inhibition of estrogen receptor (ER)-mediated genomic signaling in ER-positive cancer cells has long been a primary focus of therapeutic strategies. Here, we introduce a switchable competitive inhibition system for ERα-mediated transcriptional regulation, termed DOCTER (Drug-induced On-Off Competitor for Transcription mediated by ERα). DOCTER integrates the Tet-On induced Cre-loxP recombination system to enable precise, reversible on/off switching. We demonstrate that DOCTER effectively inhibits ERα-mediated transcriptional regulation in breast cancer cells, modulating both exogenous and endogenous gene expression, and remains effective in cells harboring ERα ligand-binding domain (LBD) mutations. Upon drug induction, DOCTER exhibits controllable and reversible inhibition. To visualize these dynamic switching events in real time, we developed a multi-color fluorescent reporting system that enables monitoring of complete DOCTER switch-off within 24 hours. Our study provides a novel approach for time-specific transcriptional regulation and offers broad potential for applications in genetic research and therapeutic development.
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