An activity-specificity trade-off encoded in human transcription factors.

ABSTRACT: Transcription factors (TFs) control specificity and activity of gene transcription, but whether a relationship between these two features exists is unclear. Here we provide evidence for an evolutionary trade-off between the activity and specificity in human TFs encoded as submaximal dispersion of aromatic residues in their intrinsically disordered protein regions. We identified approximately 500 human TFs that encode short periodic blocks of aromatic residues in their intrinsically disordered regions, resembling imperfect prion-like sequences. Mutation of periodic aromatic residues reduced transcriptional activity, whereas increasing the aromatic dispersion of multiple human TFs enhanced transcriptional activity and reprogramming efficiency, promoted liquid-liquid phase separation in vitro

SUBMITTER: Naderi J 

PROVIDER: S-EPMC11321997 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature