A model for organization and regulation of nuclear condensates by gene activity
Condensation by phase separation has recently emerged as a mechanism underlying many nuclear compartments essential for cellular functions. Nuclear condensates enrich nucleic acids and proteins, localize to specific genomic regions, and often promote gene expression. How diverse properties of nuclea...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2024
|
| Online Access: | https://hdl.handle.net/1721.1/157802 |
| _version_ | 1824458372584308736 |
|---|---|
| author | Schede, Halima H Natarajan, Pradeep Chakraborty, Arup K Shrinivas, Krishna |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Schede, Halima H Natarajan, Pradeep Chakraborty, Arup K Shrinivas, Krishna |
| author_sort | Schede, Halima H |
| collection | MIT |
| description | Condensation by phase separation has recently emerged as a mechanism underlying many nuclear compartments essential for cellular functions. Nuclear condensates enrich nucleic acids and proteins, localize to specific genomic regions, and often promote gene expression. How diverse properties of nuclear condensates are shaped by gene organization and activity is poorly understood. Here, we develop a physics-based model to interrogate how spatially-varying transcription activity impacts condensate properties and dynamics. Our model predicts that spatial clustering of active genes can enable precise localization and de novo nucleation of condensates. Strong clustering and high activity results in aspherical condensate morphologies. Condensates can flow towards distant gene clusters and competition between multiple clusters lead to stretched morphologies and activity-dependent repositioning. Overall, our model predicts and recapitulates morphological and dynamical features of diverse nuclear condensates and offers a unified mechanistic framework to study the interplay between non-equilibrium processes, spatially-varying transcription, and multicomponent condensates in cell biology. |
| first_indexed | 2025-02-19T04:24:51Z |
| format | Article |
| id | mit-1721.1/157802 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:24:51Z |
| publishDate | 2024 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1578022025-01-09T04:22:52Z A model for organization and regulation of nuclear condensates by gene activity Schede, Halima H Natarajan, Pradeep Chakraborty, Arup K Shrinivas, Krishna Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Physics Massachusetts Institute of Technology. Department of Chemistry Condensation by phase separation has recently emerged as a mechanism underlying many nuclear compartments essential for cellular functions. Nuclear condensates enrich nucleic acids and proteins, localize to specific genomic regions, and often promote gene expression. How diverse properties of nuclear condensates are shaped by gene organization and activity is poorly understood. Here, we develop a physics-based model to interrogate how spatially-varying transcription activity impacts condensate properties and dynamics. Our model predicts that spatial clustering of active genes can enable precise localization and de novo nucleation of condensates. Strong clustering and high activity results in aspherical condensate morphologies. Condensates can flow towards distant gene clusters and competition between multiple clusters lead to stretched morphologies and activity-dependent repositioning. Overall, our model predicts and recapitulates morphological and dynamical features of diverse nuclear condensates and offers a unified mechanistic framework to study the interplay between non-equilibrium processes, spatially-varying transcription, and multicomponent condensates in cell biology. 2024-12-09T21:06:45Z 2024-12-09T21:06:45Z 2023 2024-12-09T20:56:45Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/157802 Schede, H.H., Natarajan, P., Chakraborty, A.K. et al. A model for organization and regulation of nuclear condensates by gene activity. Nat Commun 14, 4152 (2023). en 10.1038/s41467-023-39878-4 Nature Communications Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Springer Nature |
| spellingShingle | Schede, Halima H Natarajan, Pradeep Chakraborty, Arup K Shrinivas, Krishna A model for organization and regulation of nuclear condensates by gene activity |
| title | A model for organization and regulation of nuclear condensates by gene activity |
| title_full | A model for organization and regulation of nuclear condensates by gene activity |
| title_fullStr | A model for organization and regulation of nuclear condensates by gene activity |
| title_full_unstemmed | A model for organization and regulation of nuclear condensates by gene activity |
| title_short | A model for organization and regulation of nuclear condensates by gene activity |
| title_sort | model for organization and regulation of nuclear condensates by gene activity |
| url | https://hdl.handle.net/1721.1/157802 |
| work_keys_str_mv | AT schedehalimah amodelfororganizationandregulationofnuclearcondensatesbygeneactivity AT natarajanpradeep amodelfororganizationandregulationofnuclearcondensatesbygeneactivity AT chakrabortyarupk amodelfororganizationandregulationofnuclearcondensatesbygeneactivity AT shrinivaskrishna amodelfororganizationandregulationofnuclearcondensatesbygeneactivity AT schedehalimah modelfororganizationandregulationofnuclearcondensatesbygeneactivity AT natarajanpradeep modelfororganizationandregulationofnuclearcondensatesbygeneactivity AT chakrabortyarupk modelfororganizationandregulationofnuclearcondensatesbygeneactivity AT shrinivaskrishna modelfororganizationandregulationofnuclearcondensatesbygeneactivity |