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BANP abre la cromatina y activa los genes regulados por la isla CpG
Ralph S Grand1, Lukas Burger1,2, Cathrin Gräwe3
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature
|July 8, 2021
Resumen
Los investigadores identificaron la proteína nuclear asociada a BTG3 (BANP) como un factor de transcripción clave para los promotores de las islas CpG. BANP activa genes esenciales y su unión está regulada por la metilación del ADN, influyendo en la estructura de la cromatina.
Área de la Ciencia:
- La genómica
- La epigenética
- Biología molecular
Sus antecedentes:
- Los promotores de la isla CpG (CGI) son los principales sitios de transcripción de la ARN polimerasa II en los mamíferos.
- La regulación de los promotores CGI es poco conocida debido al conocimiento incompleto de los factores de transcripción y sus sitios de unión funcional.
- Los motivos huérfanos, como el elemento CGCG, se encuentran cerca de los promotores activos, pero sus factores de unión son desconocidos.
Objetivo del estudio:
- Para identificar el factor de transcripción que se une al elemento CGCG.
- Para aclarar el papel de este factor de transcripción en la regulación de la expresión génica en los promotores CGI.
- Comprender cómo la metilación del ADN influye en la unión del factor de transcripción y la estructura de la cromatina.
Principales métodos:
- Huella combinada de una sola molécula con proteómica de interacción.
- Se ha investigado la unión al factor de transcripción in vitro e in vivo.
- Se analizó la accesibilidad de la cromatina y la fase de los nucleosomas en la unión del factor de transcripción.
Principales resultados:
- Identificó la proteína nuclear asociada a BTG3 (BANP) como el factor de transcripción que se une al elemento CGCG.
- BANP es un potente activador de promotores CGI, controlando los genes metabólicos esenciales en las células madre y neuronales.
- La unión de BANP es inhibida por la metilación del ADN, restringiendo su función a los IGC no metilados.
- La unión de BANP a motivos no metilados conduce a la apertura de la cromatina y la fase de los nucleosomas.
Conclusiones:
- BANP es un activador crítico de genes esenciales regulados por promotores CGI.
- La actividad del promotor CGI depende de los factores de transcripción sensibles a la metilación como BANP que pueden abrir la cromatina.
- La metilación del ADN controla epigenéticamente la unión de BANP, lo que afecta la regulación génica en las células normales y cancerosas.
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