Engineering Material Properties of Transcription Factor Condensates to Control Gene Expression in Mammalian Cells and Mice

The material properties of biomolecular condensates have a substantial impact on their function. Using optogenetics, the material properties of transcription factor condensates are systematically modulated from liquid-like toward solid-like. Liquid transcription factor condensates correlated with increased gene expression levels whereas solid-like condensates resulted in reduced gene expression levels. AbstractPhase separation of biomolecules into condensates is a key mechanism in the spatiotemporal organization of biochemical processes in cells. However, the impact of the material properties of biomolecular condensates on important processes, such as the control of gene expression, remains largely elusive. Here, the material properties of optogenetically induced transcription factor condensates are systematically tuned, and probed for their impact on the activation of target promoters. It is demonstrated that transcription factors in rather liquid condensates correlate with increased gene expression levels, whereas stiffer transcription factor condensates correlate with the opposite effect, reduced activation of gene expression. The broad nature of these findings is demonstrated in mammalian cells and mice, as well as by using different synthetic and natural transcription factors. These effects are observed for both transgenic and cell-endogenous promoters. The findings provide a novel materials-based layer in the control of gene expression, which opens novel opportunities i...
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research