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Una firma única de cromatina descubre potenciadores del desarrollo temprano en los seres humanos
Alvaro Rada-Iglesias1, Ruchi Bajpai, Tomek Swigut
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|December 17, 2010
Resumen
Los investigadores identificaron dos tipos de elementos reguladores genómicos en las células madre embrionarias humanas (hESC). Estos elementos, marcados por firmas específicas de cromatina, controlan el desarrollo humano temprano y ofrecen nuevas formas de estudiar poblaciones de células raras.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- La epigenética es la epigenética.
- La genómica es la genómica.
Sus antecedentes:
- Las transiciones de destino celular se basan en la integración de la información genómica de los elementos reguladores con el entorno celular.
- La identificación de secuencias genómicas que controlan el desarrollo embrionario humano es un desafío significativo.
Objetivo del estudio:
- Identificar y caracterizar distintas clases de elementos reguladores genómicos en las células madre embrionarias humanas (hESC).
- Comprender los mecanismos epigenéticos que gobiernan el desarrollo embrionario humano y las decisiones del destino celular.
Principales métodos:
- Inmunoprecipitación de la cromatina seguida de secuenciación (ChIP-seq) para identificar las firmas únicas de la cromatina.
- Análisis de las modificaciones histónicas (H3K4me1, H3K27ac, H3K27me3) y los reguladores de la cromatina (p300, BRG1).
- Ensayos funcionales en embriones de pez cebra para evaluar la actividad del potenciador.
Principales resultados:
- Se identificaron dos clases distintas de elementos genómicos en los hESC, caracterizados por marcas y reguladores específicos de la cromatina.
- Los elementos de clase 1 son potenciadores activos asociados con genes expresados por hESC.
- Los "potenciadores de equilibrio" de la clase 2 están vinculados a genes de desarrollo inactivos y adquieren marcas activas al diferenciarse, dirigiendo la expresión específica del tipo celular y la etapa.
Conclusiones:
- Los potenciadores del desarrollo temprano están epigenéticamente marcados previamente en los hESC, con potenciadores en equilibrio que juegan un papel clave en la embriogénesis temprana.
- H3K27me3 tiene un papel poco apreciado en los elementos reguladores distantes durante el desarrollo temprano.
- Las secuencias reguladoras identificadas proporcionan un recurso para el estudio de poblaciones de células transitorias y raras en la embriogénesis humana temprana.
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