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Una región de control global define un paisaje regulador cromosómico que contiene el grupo HoxD
François Spitz1, Federico Gonzalez, Denis Duboule
1Department of Zoology and Animal Biology, NCCR Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Cell
|May 7, 2003
Resumen
Los investigadores identificaron una región de ADN conservada que controla la expresión del gen Hoxd durante el desarrollo de las extremidades. Esta región actúa como un gran dominio regulador, influyendo en múltiples genes y interrumpido por la mutación Ulnaless.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La expresión genética Hoxd coordinada es crucial para el desarrollo de las extremidades, particularmente en el desarrollo de los dedos.
- Comprender los mecanismos reguladores que controlan estos genes es esencial para descifrar los procesos de desarrollo.
Objetivo del estudio:
- Identificar las secuencias de ADN reguladoras que controlan la expresión génica Hoxd en el desarrollo de las extremidades.
- Para investigar la función de un gen recién identificado, Lunapark (Lnp), y su relación con los genes Hoxd y Evx2.2.
Principales métodos:
- Utilizó un enfoque de enhancer-trap dirigido para identificar segmentos de ADN con patrones de expresión específicos.
- Analizó la conservación del ADN entre especies, incluso con secuencias de peces globo.
- Investigó el impacto de la mutación de Ulnaless (una inversión equilibrada) en la regulación génica.
Principales resultados:
- Descubrió una región de ADN aguas arriba del grupo Hoxd que dirige la expresión génica del reportero en los dígitos y el SNC, reflejando los patrones Lnp, Evx2 y Hoxd.
- Esta región exhibe una importante conservación interespecífica y contiene un grupo de potenciadores globales.
- Estos potenciadores definen grandes dominios reguladores que son interrumpidos por la mutación Ulnaless.
Conclusiones:
- Identificó un nuevo dominio regulador que controla múltiples genes, incluidos los genes Hoxd, durante el desarrollo de las extremidades y el SNC.
- Los hallazgos sugieren un modelo de regulación específica del locus en lugar de un control exclusivo específico del gen.
- La naturaleza conservada de este dominio regulador resalta su importancia en el desarrollo de los vertebrados.
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