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El núcleo líquido se condensa mecánicamente y reestructura el genoma
Yongdae Shin1, Yi-Che Chang2, Daniel S W Lee3
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, South Korea.
Cell
|December 1, 2018
Resumen
La separación de la fase líquida biomolecular en el núcleo excluye mecánicamente la cromatina, favoreciendo regiones más suaves y eucromáticas. El ADN objetivo se puede unir por coalescencia de condensado, actuando como filtros mecanoactivos.
Área de la Ciencia:
- Biología celular
- La biofísica
- La genómica
Sus antecedentes:
- La organización intracelular se basa en las transiciones de fase líquida biomolecular.
- La separación de fase líquido-líquido de proteínas intrínsecamente desordenadas (IDP) impulsa la formación de cuerpos nucleares.
- No se comprende bien la influencia mecánica de estos condensados en la estructura de la cromatina.
Objetivo del estudio:
- Investigar cómo las fuerzas físicas de los condensados líquidos reestructuran la cromatina.
- Explorar el papel de las propiedades mecánicas en la formación de condensados y la organización de la cromatina.
Principales métodos:
- Utilizó CasDrop, una tecnología optogenética basada en CRISPR-Cas9.
- Separación de fase observada de varios IDP en condensados líquidos.
- Desarrolló un modelo físico mínimo para explicar el comportamiento del condensado.
Principales resultados:
- Los condensados IDP excluyen mecánicamente la cromatina a medida que crecen.
- Los condensados se forman preferentemente en regiones eucromáticas de baja densidad debido a la sensibilidad a la rigidez.
- La coalescencia impulsada por la tensión superficial puede unir mecánicamente los loci genómicos seleccionados.
Conclusiones:
- Los condensados nucleares actúan como filtros de cromatina mecanoactivos.
- Estos condensados manipulan físicamente la cromatina excluyendo regiones no dirigidas y concentrando loci dirigidos.
- La separación de fase influye en la organización nuclear a través de fuerzas mecánicas en la cromatina.
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