Liquid-liquid phase separation of light-inducible transcription factors increases transcription activation in mammalian cells and mice.

ABSTRACT: Light-inducible gene switches represent a key strategy for the precise manipulation of cellular events in fundamental and applied research. However, the performance of widely used gene switches is limited due to low tissue penetrance and possible phototoxicity of the light stimulus. To overcome these limitations, we engineer optogenetic synthetic transcription factors to undergo liquid-liquid phase separation in close spatial proximity to promoters. Phase separation of constitutive and optogenetic synthetic transcription factors was achieved by incorporation of intrinsically disordered regions. Supported by a quantitative mathematical model, we demonstrate that engineered transcription factor droplets form at target promoters and increase gene expression up to fivefold. This increase in pe

SUBMITTER: Schneider N 

PROVIDER: S-EPMC7775772 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature