High-throughput Oligopaint screen identifies druggable 3D genome regulators.
Nature
; 620(7972): 209-217, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-37438531
ABSTRACT
The human genome functions as a three-dimensional chromatin polymer, driven by a complex collection of chromosome interactions1-3. Although the molecular rules governing these interactions are being quickly elucidated, relatively few proteins regulating this process have been identified. Here, to address this gap, we developed high-throughput DNA or RNA labelling with optimized Oligopaints (HiDRO)-an automated imaging pipeline that enables the quantitative measurement of chromatin interactions in single cells across thousands of samples. By screening the human druggable genome, we identified more than 300 factors that influence genome folding during interphase. Among these, 43 genes were validated as either increasing or decreasing interactions between topologically associating domains. Our findings show that genetic or chemical inhibition of the ubiquitous kinase GSK3A leads to increased long-range chromatin looping interactions in a genome-wide and cohesin-dependent manner. These results demonstrate the importance of GSK3A signalling in nuclear architecture and the use of HiDRO for identifying mechanisms of spatial genome organization.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatina
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Genoma Humano
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Cromossomos Humanos
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Quinases da Glicogênio Sintase
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Posicionamento Cromossômico
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Ensaios de Triagem em Larga Escala
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Análise de Célula Única
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article