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

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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 mm), but burst size and frequency are enhanced when the condensate moves in proximity (<1 mm). 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.
Publisher
CELL PRESS
Issue Date
2024-01
Language
English
Article Type
Article
Citation

CELL, v.187, no.2

ISSN
0092-8674
DOI
10.1016/j.cell.2023.12.005
URI
http://hdl.handle.net/10203/319740
Appears in Collection
BS-Journal Papers(저널논문)
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