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Peer-reviewedCC BY-NCCell Reports

Emergent 3D genome reorganization and graded gene control from the stepwise assembly of transcriptional condensates

  • Surabhi Chowdhary1
  • Sarah Paracha2
  • Lucas Dyer2
  • David Pincus3
  1. 1Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA. Electronic address: [email protected]
  2. 2Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA
  3. 3Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL, USA; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA; Center for Physics of Evolution, University of Chicago, Chicago, IL, USA. Electronic address: [email protected]
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Abstract

Transcriptional condensates are clusters of transcription factors, coactivators, and RNA Pol II associated with gene activation, yet how they assemble and function within the cell remains unclear. Here, we show that transcriptional condensates form in a stepwise manner to enable both graded and three-dimensional (3D) gene control in the yeast heat shock response (HSR). First, the transcription factor Hsf1 (heat shock factor 1) clusters upon partial dissociation from the chaperone Hsp70. Next, the coactivator Mediator partitions following further Hsp70 dissociation and Hsf1 phosphorylation. Finally, Pol II condenses, driving emergent coalescence of HSR genes. Separation-of-function Hsf1 mutants revealed graded (non-switch-like) control of transcription and a decoupling of condensate formation and gene activation. Fully assembled HSR condensates promoted adaptive 3D genome reconfiguration, suggesting a role beyond transcription. In the HSR, differential condensation of the transcriptional machinery quantitatively tunes gene expression and qualitatively remodels the 3D genome.

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Cite

BibTeXRIS
BibTeX
@article{chowdhary2026emergent,
  title = {{Emergent 3D genome reorganization and graded gene control from the stepwise assembly of transcriptional condensates}},
  author = {Surabhi Chowdhary and Sarah Paracha and Lucas Dyer and David Pincus},
  journal = {Cell Reports},
  year = {2026},
  month = aug,
  doi = {10.1016/j.celrep.2026.117888},
  url = {https://doi.org/10.1016/j.celrep.2026.117888},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Emergent 3D genome reorganization and graded gene control from the stepwise assembly of transcriptional condensates
AU  - Surabhi Chowdhary
AU  - Sarah Paracha
AU  - Lucas Dyer
AU  - David Pincus
PY  - 2026
DA  - 2026/08/22
JO  - Cell Reports
DO  - 10.1016/j.celrep.2026.117888
UR  - https://doi.org/10.1016/j.celrep.2026.117888
AB  - Transcriptional condensates are clusters of transcription factors, coactivators, and RNA Pol II associated with gene activation, yet how they assemble and function within the cell remains unclear. Here, we show that transcriptional condensates form in a stepwise manner to enable both graded and three-dimensional (3D) gene control in the yeast heat shock response (HSR). First, the transcription factor Hsf1 (heat shock factor 1) clusters upon partial dissociation from the chaperone Hsp70. Next, the coactivator Mediator partitions following further Hsp70 dissociation and Hsf1 phosphorylation. Finally, Pol II condenses, driving emergent coalescence of HSR genes. Separation-of-function Hsf1 mutants revealed graded (non-switch-like) control of transcription and a decoupling of condensate formation and gene activation. Fully assembled HSR condensates promoted adaptive 3D genome reconfiguration, suggesting a role beyond transcription. In the HSR, differential condensation of the transcriptional machinery quantitatively tunes gene expression and qualitatively remodels the 3D genome.
SN  - 2211-1247
SN  - 2639-1856
ER  -