Transcription activation is enhanced by multivalent interactions independent of phase separation
Open accessPublished version of a preprint
Abstract
Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving phase separation into transcriptional condensates. Here, we dissected transcription activation by comparing different synthetic TFs at a reporter gene array with real-time single-cell fluorescence microscopy. In these experiments, binding site occupancy, residence time, and coactivator recruitment in relation to multivalent TF interactions were compared. While phase separation propensity and activation strength of the AD were linked, the actual formation of liquid-like TF droplets had a neutral or inhibitory effect on transcription activation. We conclude that multivalent AD-mediated interactions enhance the transcription activation capacity of a TF by increasing its residence time in the chromatin-bound state and facilitating the recruitment of coactivators independent of phase separation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Current theories propose liquid-liquid phase separation and some form of transcription factor trapping or engagement of transcription factors in multivalent interactions independent of assembly into phase-separated liquid-like droplets.
“current theories propose liquid-liquid phase separation18,64–66 and some form of TF trapping22,67 or engagement of TFs in multivalent interactions independent of assembly into phase-separated liquid-like droplets.68”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 4
- [1]1. Banani, S.F. ∙ Lee, H.O. ∙ Hyman, A.A. ... Biomolecular condensates: Organizers of cellular biochemistry Nat. Rev. Mol. Cell Biol. 2017; 18:285-298 Crossref Scopus (3254) PubMed Google Scholar
- [2]2. Boija, A. ∙ Klein, I.A. ∙ Sabari, B.R. ... Transcription factors activate genes through the phase-separation capacity of their activation domains Cell. 2018; 175:1842-1855.e16 Full Text Full Text (PDF) Scopus (1024) PubMed Google Scholar
- [3]3. Bracha, D. ∙ Walls, M.T. ∙ Wei, M.T. ... Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds Cell. 2018; 175:1467-1480.e13 Full Text Full Text (PDF) Scopus (282) PubMed Google Scholar
- [4]4. Brent, R. ∙ Ptashne, M. A eukaryotic transcriptional activator bearing the DNA specificity of a prokaryotic repressor Cell. 1985; 43:729-736
Cited by
Sorted by citations
Hsieh, T.-H. S., Cattoglio, C., Slobodyanyuk, E., Hansen, A. S., Darzacq, X., & Tjian, R. (2022) · Nature Genetics · doi:10.1038/s41588-022-01223-8 · Cited by 406 · see citing works
Super-enhancers include classical enhancers and facilitators to fully activate gene expression
Blayney, J. W., Francis, H., Rampasekova, A., Camellato, B., Mitchell, L., Stolper, R., Cornell, L., Babbs, C., Boeke, J. D., Higgs, D. R., et al. (2023) · Cell · doi:10.1016/j.cell.2023.11.030 · Cited by 196 · see citing works
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation
Yang, J. H., & Hansen, A. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00710-6 · Cited by 191 · see citing works
- Authors
- Trojanowski, J., Frank, L., Rademacher, A., Mücke, N., Grigaitis, P., & Rippe, K.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Rippe, Karsten
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 82
- Issue
- 10
- Pages
- 1878-1893.e10
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W4229375645
- Cited by
- 232
- References
- 0
- Citations by year
- 2026: 36 · 2025: 49 · 2024: 60 · 2023: 48 · 2022: 29 · 2021: 10
- FWCI
- 15.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 383 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (INST 35/1314-1 FUGG, INST 35/1503-1 FUGG)
- Deutsche Forschungsgemeinschaft (RI1283/16-1)
- Universität Heidelberg
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- transcriptional activation, multivalent interactions, phase separation, transcriptional condensates, coactivator recruitment, chromatin binding, binding site occupancy, residence time, synthetic transcription factors, liquid-like droplets
- MeSH terms
- Protein Domains, Binding Sites, Chromatin, Transcription Factors, Transcriptional Activation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
