The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Nucleated transcriptional condensates amplify gene expression
Open accessAbstract
Membraneless organelles or condensates form through liquid–liquid phase separation1–4, which is thought to underlie gene transcription through condensation of the large-scale nucleolus5–7 or in smaller assemblies known as transcriptional condensates8–11. Transcriptional condensates have been hypothesized to phase separate at particular genomic loci and locally promote the biomolecular interactions underlying gene expression. However, there have been few quantitative biophysical tests of this model in living cells, and phase separation has not yet been directly linked with dynamic transcriptional outputs12,13. Here, we apply an optogenetic approach to show that FET-family transcriptional regulators exhibit a strong tendency to phase separate within living cells, a process that can drive localized RNA transcription. We find that TAF15 has a unique charge distribution among the FET family members that enhances its interactions with the C-terminal domain of RNA polymerase II. Nascent C-terminal domain clusters at primed genomic loci lower the energetic barrier for nucleation of TAF15 condensates, which in turn further recruit RNA polymerase II to drive transcriptional output. These results suggest that positive feedback between interacting transcriptional components drives localized phase separation to amplify gene expression. Wei et al. show that clusters of unphosphorylated RNA polymerase II seed the nucleation of phase-separated condensates of TAF15, which further recruit RNA polymerase II to amplify transcriptional activation.
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Cites
Biomolecular condensates: organizers of cellular biochemistry
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Liquid phase condensation in cell physiology and disease
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Self-citationA Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation
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Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation
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Self-citationCoactivator condensation at super-enhancers links phase separation and gene control
Sabari, B. R., Dall’Agnese, A., Boija, A., Klein, I. A., Coffey, E. L., Shrinivas, K., Abraham, B. J., Hannett, N. M., Zamudio, A. V., Manteiga, J. C., et al. (2018) · Science · doi:10.1126/science.aar3958 · Cited by 2,595
Phase transitions in the assembly of multivalent signalling proteins
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Coexisting Liquid Phases Underlie Nucleolar Subcompartments
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Self-citationBoija, A., Klein, I. A., Sabari, B. R., Dall’Agnese, A., Coffey, E. L., Zamudio, A. V., Li, C. H., Shrinivas, K., Manteiga, J. C., Hannett, N. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.042 · Cited by 1,815
Cited by
The nucleolus as a multiphase liquid condensate
Lafontaine, D. L. J., Riback, J. A., Bascetin, R., & Brangwynne, C. P. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0272-6 · Cited by 1,051
Self-citationPartitioning of cancer therapeutics in nuclear condensates
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Self-citationAdvances in Targeting ‘Undruggable’ transcription Factors With Small Molecules
Henley, M. J., & Koehler, A. N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00199-0 · Cited by 409
Modulating biomolecular condensates: a novel approach to drug discovery
Mitrea, D. M., Mittasch, M., Gomes, B. F., Klein, I. A., & Murcko, M. A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00505-4 · Cited by 401
Capillary forces generated by biomolecular condensates
Gouveia, B., Kim, Y., Shaevitz, J. W., Petry, S., Stone, H. A., & Brangwynne, C. P. (2022) · Nature · doi:10.1038/s41586-022-05138-6 · Cited by 270
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Metadata
- Authors
- Wei, M.-T., Chang, Y.-C., Shimobayashi, S. F., Shin, Y., Strom, A. R., & Brangwynne, C. P.
- Venue
- Nature Cell Biology
- Published
- 2020-09-14
- Volume
- 22
- Issue
- 10
- Pages
- 1187-1196
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W3085471727
- Cited by
- 328
- References
- 61
- FWCI
- 11.55
- Type
- journal article
- Language
- en
- Open access
- green
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