YAP charge patterning mediates signal integration through transcriptional co-condensates
Kirstin Meyer1,2, Klaus Yserentant2,3, Rasmi Cheloor-Kovilakam2,3
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Biorxiv : the Preprint Server for Biology
|August 16, 2024
Summary
YAP and Mediator proteins form transcriptionally active condensates in stem cells. Specific charge patterns on YAP, not net charge, drive this interaction, enabling adaptive gene regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biophysics
Background:
- Transcription factor dynamics regulate gene expression.
- Biomolecular condensates are key signaling platforms, but their mechanisms are unclear.
- Understanding YAP signal integration in transcriptional condensates is crucial.
Purpose of the Study:
- To investigate the molecular mechanisms of YAP signal integration within transcriptional condensates.
- To elucidate how YAP and Mediator co-condense and regulate gene transcription.
- To reveal the role of YAP condensate formation in adaptive gene regulatory responses.
Main Methods:
- Light-sheet single-molecule imaging in stem cells.
- Construction and analysis of synthetic condensates.
- Intrinsically disordered region (IDR) sequence analysis and protein engineering of YAP.
Main Results:
- Demonstrated charge-mediated co-condensation of YAP and Mediator into transcriptionally active condensates.
- Identified YAP's negative charge patterning, not net charge, as critical for specific interaction with Mediator's positive charge blocks.
- Observed that transcription-induced negative feedback counteracts YAP/Mediator co-condensation, leading to adaptive responses.
Conclusions:
- Established a molecular framework for YAP condensate formation.
- Revealed that YAP condensate dynamics facilitate adaptive transcriptional responses to dynamic inputs.
- Provided new insights into the function of YAP condensates in emergent gene regulatory behavior.
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