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Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
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Imágenes a escala genómica de la organización 3D y la actividad transcripcional de la cromatina
Jun-Han Su1, Pu Zheng1, Seon S Kinrot2
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, and Department of Physics, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Cell
|August 22, 2020
Resumen
Los investigadores desarrollaron una nueva tecnología de imagen para visualizar la organización del genoma en 3D en células individuales. Este método mapea la conformación de la cromatina y la actividad génica a través de múltiples escalas, ofreciendo información sobre la regulación del genoma.
Área de la Ciencia:
- La genómica
- Biología molecular
- Biología celular
- Tecnología de imágenes
Sus antecedentes:
- La organización tridimensional (3D) de la cromatina es crucial para regular diversas funciones del genoma.
- La comprensión actual de la arquitectura del genoma 3D requiere herramientas avanzadas para la visualización directa dentro del entorno celular nativo.
Objetivo del estudio:
- Introducir y validar una nueva tecnología de imagen para visualizar la organización de la cromatina en múltiples escalas en células individuales.
- Para lograr un alto rendimiento genómico para el seguimiento y análisis detallado de la conformación de la cromatina.
Principales métodos:
- Imágenes multiplexadas de cientos de loci genómicos utilizando hibridación secuencial para el rastreo de conformación de alta resolución.
- Desarrollo y aplicación de la hibridación in situ por fluorescencia multiplexada resistente a errores (MERFISH) para el rastreo de la cromatina a escala genómica.
- Imágenes simultáneas de más de 1.000 loci genómicos, transcripciones nacientes y estructuras nucleares.
Principales resultados:
- Se ha demostrado el rastreo de conformación de cromosomas enteros en alta resolución.
- Se obtuvieron con éxito imágenes de más de 1.000 loci genómicos y transcripciones nacientes simultáneamente.
- Dominios de cromatina de una sola célula caracterizados, compartimentos, interacciones transcromosómicas y su vínculo con la transcripción.
Conclusiones:
- La tecnología de imagen de alto rendimiento, multiescala y multimodal desarrollada proporciona una visión integrada de la organización de la cromatina.
- Esta tecnología ofrece información sin precedentes sobre el contexto estructural y funcional del genoma en su estado nativo.
- Se prevén amplias aplicaciones para avanzar en el estudio de la regulación y la función del genoma.
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