YAP charge patterning mediates signal integration through transcriptional co-condensates
Abstract Transcription factor dynamics are used to selectively engage gene regulatory programs. Biomolecular condensates have emerged as an attractive signaling module in this process, but the underlying mechanisms are not well-understood. Here, we probe the molecular basis of YAP signal integration...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62157-3 |
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| author | Kirstin Meyer Klaus Yserentant Rasmi Cheloor-Kovilakam Kiersten M. Ruff Chan-I Chung Xiaokun Shu Bo Huang Orion D. Weiner |
| author_facet | Kirstin Meyer Klaus Yserentant Rasmi Cheloor-Kovilakam Kiersten M. Ruff Chan-I Chung Xiaokun Shu Bo Huang Orion D. Weiner |
| author_sort | Kirstin Meyer |
| collection | DOAJ |
| description | Abstract Transcription factor dynamics are used to selectively engage gene regulatory programs. Biomolecular condensates have emerged as an attractive signaling module in this process, but the underlying mechanisms are not well-understood. Here, we probe the molecular basis of YAP signal integration through transcriptional condensates. Leveraging light-sheet single-molecule imaging and synthetic condensates, we demonstrate charge-mediated co-condensation of the transcriptional regulators YAP and Mediator into transcriptionally active condensates in stem cells. Intrinsically disordered region sequence analysis and YAP protein engineering demonstrate that the signaling specificity of YAP is established, in part, through complementary electrostatic interactions between negatively charged blocks within YAP and positively charged blocks within Mediator. YAP/Mediator co-condensation is counteracted by negative feedback from transcription, driving an adaptive transcriptional response that is well-suited for decoding dynamic inputs. Our work reveals a molecular framework for YAP condensate formation and sheds light on the function of YAP condensates for emergent gene regulatory behavior. |
| format | Article |
| id | doaj-art-d76779e0848f414ab29fd4fe1dad91bd |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d76779e0848f414ab29fd4fe1dad91bd2025-08-20T03:46:28ZengNature PortfolioNature Communications2041-17232025-08-0116111610.1038/s41467-025-62157-3YAP charge patterning mediates signal integration through transcriptional co-condensatesKirstin Meyer0Klaus Yserentant1Rasmi Cheloor-Kovilakam2Kiersten M. Ruff3Chan-I Chung4Xiaokun Shu5Bo Huang6Orion D. Weiner7Cardiovascular Research Institute, University of California, San FranciscoDepartment of Pharmaceutical Chemistry, University of California, San FranciscoDepartment of Pharmaceutical Chemistry, University of California, San FranciscoDepartment of Biomedical Engineering and Center for Biomolecular Condensates, James McKelvey School of Engineering, Washington University in St. LouisCardiovascular Research Institute, University of California, San FranciscoCardiovascular Research Institute, University of California, San FranciscoDepartment of Biochemistry and Biophysics, University of California, San FranciscoCardiovascular Research Institute, University of California, San FranciscoAbstract Transcription factor dynamics are used to selectively engage gene regulatory programs. Biomolecular condensates have emerged as an attractive signaling module in this process, but the underlying mechanisms are not well-understood. Here, we probe the molecular basis of YAP signal integration through transcriptional condensates. Leveraging light-sheet single-molecule imaging and synthetic condensates, we demonstrate charge-mediated co-condensation of the transcriptional regulators YAP and Mediator into transcriptionally active condensates in stem cells. Intrinsically disordered region sequence analysis and YAP protein engineering demonstrate that the signaling specificity of YAP is established, in part, through complementary electrostatic interactions between negatively charged blocks within YAP and positively charged blocks within Mediator. YAP/Mediator co-condensation is counteracted by negative feedback from transcription, driving an adaptive transcriptional response that is well-suited for decoding dynamic inputs. Our work reveals a molecular framework for YAP condensate formation and sheds light on the function of YAP condensates for emergent gene regulatory behavior.https://doi.org/10.1038/s41467-025-62157-3 |
| spellingShingle | Kirstin Meyer Klaus Yserentant Rasmi Cheloor-Kovilakam Kiersten M. Ruff Chan-I Chung Xiaokun Shu Bo Huang Orion D. Weiner YAP charge patterning mediates signal integration through transcriptional co-condensates Nature Communications |
| title | YAP charge patterning mediates signal integration through transcriptional co-condensates |
| title_full | YAP charge patterning mediates signal integration through transcriptional co-condensates |
| title_fullStr | YAP charge patterning mediates signal integration through transcriptional co-condensates |
| title_full_unstemmed | YAP charge patterning mediates signal integration through transcriptional co-condensates |
| title_short | YAP charge patterning mediates signal integration through transcriptional co-condensates |
| title_sort | yap charge patterning mediates signal integration through transcriptional co condensates |
| url | https://doi.org/10.1038/s41467-025-62157-3 |
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