Direct observation of a condensate effect on super-enhancer controlled gene bursting.
Cell
; 187(2): 331-344.e17, 2024 01 18.
Article
em En
| MEDLINE
| ID: mdl-38194964
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Regulação da Expressão Gênica
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Fatores de Transcrição SOXB1
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Super Intensificadores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha