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Journal Article

Direct observation of a condensate effect on super-enhancer controlled gene bursting

MPS-Authors
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Du,  Manyu
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Stitzinger,  Simon Hendrik
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Spille,  Jan-Hendrik
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Cho,  Won-Ki
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Lee,  Choongman
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hijaz,  Mohammed
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Quintana,  Andrea
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons289417

Cissé,  Ibrahim Ibrahim
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.sciencedirect.com/science/article/pii/S0092867423013375?via%3Dihub
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Fulltext (public)

10.1016_j.cell.2023.12.005.pdf
(Publisher version), 8MB

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Citation

Du, M., Stitzinger, S. H., Spille, J.-H., Cho, W.-K., Lee, C., Hijaz, M., et al. (2024). Direct observation of a condensate effect on super-enhancer controlled gene bursting. Cell, 187, 331-344. doi:10.1016/j.cell.2023.12.005.


Cite as: https://hdl.handle.net/21.11116/0000-000E-38F7-D
Abstract
Enhancers are distal DNA elements believed to loop and contact promoters to control gene expression. Recently, we found diffraction-sized transcriptional condensates at genes controlled by clusters of enhancers (super-enhancers). However, a direct function of endogenous condensates in controlling gene expression remains elusive. Here, we develop live-cell super-resolution and multi-color 3D-imaging approaches to investigate putative roles of endogenous condensates in the regulation of super-enhancer controlled gene Sox2. In contrast to enhancer distance, we find instead that the condensate's positional dynamics are a better predictor of gene expression. A basal gene bursting occurs when the condensate is far (>1 μm), but burst size and frequency are enhanced when the condensate moves in proximity (<1 μm). Perturbations of cohesin and local DNA elements do not prevent basal bursting but affect the condensate and its burst enhancement. We propose a three-way kissing model whereby the condensate interacts transiently with gene locus and regulatory DNA elements to control gene bursting.