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Los factores de transcripción pioneros se dirigen a motivos parciales de ADN en los nucleosomas para iniciar la
Abdenour Soufi1, Meilin Fernandez Garcia1, Artur Jaroszewicz2
1Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Smilow Center for Translational Research, Building 421, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA.
Cell
|April 21, 2015
Resumen
Los factores de transcripción pioneros (TF) utilizan dominios de unión al ADN para acceder a la cromatina silenciosa, iniciando cambios en el destino celular. Su capacidad para unir nucleosomas y reconocer motivos parciales de ADN en su superficie impulsa este proceso crucial.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- Biología celular Biología celular.
Sus antecedentes:
- Los factores de transcripción pioneros (TF) son cruciales para iniciar cambios en el destino celular al acceder a la cromatina silenciosa.
- FoxA, un TF pionero bien estudiado, utiliza un dominio de unión de ADN de hélice alado (DBD) para unirse a los nucleosomas y la cromatina compactada.
- Comprender los mecanismos de otros TF pioneros es esencial para comprender la reprogramación celular.
Objetivo del estudio:
- Para comparar las actividades de orientación de nucleosomas y cromatina de Oct4, Sox2, Klf4 y c-Myc.
- Investigar el papel de los dominios de unión al ADN (DBD) en la actividad pionera de estos factores.
- Para dilucidar cómo estos factores reprograman colectivamente las células somáticas a la pluripotencia.
Principales métodos:
- Ensayos de unión in vitro con proteínas purificadas Oct4, Sox2 y Klf4.
- Análisis de orientación de la cromatina in vivo.
- Análisis comparativo de las estructuras y funciones del dominio de unión del ADN.
Principales resultados:
- Las proteínas Oct4, Sox2 y Klf4 demostraron capacidades de unión de nucleosomas in vitro.
- Estos factores se dirigieron preferentemente a sitios silenciosos de cromatina enriquecidos con nucleosomas in vivo.
- La actividad pionera se correlacionó con la capacidad del DBD para reconocer motivos parciales de ADN en los nucleosomas.
- La vinculación coordinada entre factores facilita el reconocimiento parcial de motivos.
Conclusiones:
- La capacidad de los TF pioneros para unirse a los nucleosomas y reconocer motivos parciales de ADN en su superficie es clave para su función.
- Estos mecanismos proporcionan información sobre cómo los factores pioneros acceden y modifican la cromatina ingenua.
- Comprender estas interacciones es vital para el avance de la reprogramación celular y la medicina regenerativa.
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