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Los potenciadores ultraconservados son necesarios para el desarrollo normal

Diane E Dickel1, Athena R Ypsilanti2, Ramón Pla2

  • 1Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.

Cell
|January 24, 2018
PubMed
Resumen
Este resumen es generado por máquina.

Los potenciadores ultraconservados son cruciales para el desarrollo normal de los mamíferos. La eliminación de estas secuencias cerca del gen Arx en ratones causó sutiles defectos neurológicos y de crecimiento, revelando su importancia oculta.

Palabras clave:
Arx también.desarrollo del cerebromejoradorregulación genéticaEl hipocampoen vivoEl nocaut.Las neuronasNo codificadoultraconservados

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Área de la Ciencia:

  • La genómica
  • Biología del desarrollo
  • La neurociencia

Sus antecedentes:

  • Las regiones ultraconservadas no codificantes (UCR) son secuencias altamente conservadas en los genomas de mamíferos.
  • Estos UCR pueden actuar como potenciadores de acción remota, regulando la expresión génica.
  • Estudios anteriores no mostraron un impacto inmediato de la deleción de UCR en la viabilidad.

Objetivo del estudio:

  • Investigar el papel de los potenciadores ultraconservados en el desarrollo normal.
  • Para determinar la importancia funcional de las UCR específicas ubicadas cerca del gen Arx.

Principales métodos:

  • Utilizó la edición del genoma para crear ratones knockout que carecen de UCRs individuales o en combinación.
  • Centrado en los UCR más largos en todo el genoma, particularmente los cercanos al gen Arx.
  • Analizó los fenotipos neurológicos y de crecimiento en ratones mutantes.

Principales resultados:

  • Los ratones con deleciones UCR individuales o en pares fueron viables y fértiles.
  • Casi todos los ratones mutantes exhibieron anomalías neurológicas y defectos de crecimiento.
  • Se observaron alteraciones sustanciales en las poblaciones de neuronas y defectos estructurales del cerebro.

Conclusiones:

  • Los potenciadores ultraconservados son esenciales para el desarrollo normal de los mamíferos.
  • La fuerte conservación de la secuencia en los UCR probablemente refleje déficits de aptitud no aparentes en condiciones estándar de laboratorio.
  • Estos hallazgos ponen de relieve la importancia funcional de las UCR en el desarrollo y la evolución.