A Tet/Q Hybrid System for Robust and Versatile Control of Transgene Expression in C. elegans

Binary gene regulatory tools such as the Tetracycline (Tet)-controlled transcription system have revolutionized genetic research in multiple organisms, but their applications to the worm remain very limited. Here we report that the canonical Tet system is largely inactive in the worm but can be adapted for the worm by introducing multiple modifications, a crucial one being the use of the transcription activation domain from the fungal Q binary system. The resultant Tet/Q hybrid system proves more robust and flexible than either of its precursors, enabling elaborate modes of transgene manipulation previously hard to achieve in the worm, including inducible intersectional regulation and, in combination with the Q system, independent control of distinct transgenes within the same cells. Furthermore, we demonstrated, as an example of its applications, that the hybrid system can tightly and efficiently control Cre expression. This study establishes Tet/Q as a premier binary system for worm genetic research. [Display omitted] •The popular Tet-controlled gene regulatory system proves inapplicable to the worm•The fungal Q binary gene regulatory system is moderately active in the worm•A hybrid Tet/Q system is capable of robust, rapid and tunable transgene induction•Further modifications enable sophisticated regulation previously hard to achieve Genetics; Techniques in Genetics; Model Organism