Molecular Mechanisms of Transcription Factors with Dual Activator and Repressor Functions

Transcription factors (TFs) are traditionally classified as activators or repressors, yet some can perform both roles. We highlight well-supported examples of dual activator/repressor functions and review the mechanisms that explain how duality arises. These examples reveal that transcriptional duality arises from three recurring mechanisms: positional effects, cofactor exchange, and regulatory switches. Even within these recurring mechanisms, the precise molecular details diverge, with regulatory outcomes dictated by differences in TF positioning, cofactor availability, modification state, and ligand binding. We propose that future work should move beyond descriptive labels of context specificity and instead focus on elucidating the precise molecular mechanisms by which TFs function to elicit opposing regulatory effects.