Systematic Evaluation and Application of IDR Domain-Mediated Transcriptional Activation of NUP98 in Saccharomyces cerevisiae

Implementing dynamic control over gene transcription to decouple cell growth is essential for regulating protein expression in microbial cells. However, the availability of efficient regulatory elements in Saccharomyces cerevisiae remains limited. In this study, we present a novel β-estradiol-inducible gene expression system, termed DEN. This system combines a DNA-binding domain with an estradiol-binding domain and an intrinsically disordered region (IDR) from NUP98. Comparative analysis shows that the DEN system outperforms IDRs from other proteins, achieving an approximately 60-fold increase in EGFP expression upon β-estradiol induction. Moreover, our system is tightly controlled; nontoxic gene expression makes it a powerful tool for rapid and precise modulation of target gene expression. This system holds great potential for unlocking new functionalities from existing proteins in future research.