YAP charge patterning mediates signal integration through transcriptional co-condensates
Kirstin Meyer1,2, Klaus Yserentant3, Rasmi Cheloor-Kovilakam3
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, 94158, USA.
Nature Communications
|August 12, 2025
Summary
Scientists uncovered how YAP and Mediator proteins form transcriptionally active condensates in stem cells. This charge-mediated process allows for adaptive gene regulation in response to dynamic signals.
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Transcription factors regulate gene expression through dynamic interactions.
- Biomolecular condensates are emerging as key signaling modules in gene regulation.
- The precise mechanisms of YAP signal integration within condensates are not fully understood.
Purpose of the Study:
- To investigate the molecular basis of YAP signal integration within transcriptional condensates.
- To elucidate the role of YAP and Mediator co-condensation in gene regulation.
- To understand the adaptive transcriptional response driven by YAP condensates.
Main Methods:
- Light-sheet single-molecule imaging.
- Construction and analysis of synthetic condensates.
- Intrinsically disordered region sequence analysis.
- YAP protein engineering.
Main Results:
- Demonstrated charge-mediated co-condensation of YAP and Mediator into transcriptionally active condensates in stem cells.
- Identified complementary electrostatic interactions between YAP and Mediator as critical for specificity.
- Revealed that YAP/Mediator co-condensation is regulated by negative feedback from transcription, enabling adaptive responses.
Conclusions:
- Established a molecular framework for YAP condensate formation.
- Showcased the function of YAP condensates in emergent gene regulatory behavior.
- Highlighted the role of electrostatic interactions and negative feedback in YAP-mediated transcriptional regulation.
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