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La expresión génica y la identidad celular controladas por el complejo promotor de la anafase

Eugene Oh1,2, Kevin G Mark1,2, Annamaria Mocciaro1,2,3

  • 1Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA, USA.

Nature
|February 21, 2020
PubMed
Resumen

Los científicos descubrieron un mecanismo dependiente de la ubiquitina que reinicia la expresión génica después de la división celular. Este proceso, que involucra al complejo promotor de la anafase (APC/C), asegura que la identidad celular se mantenga a través de los ciclos celulares.

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Área de la Ciencia:

  • Biología celular
  • Biología molecular
  • Biología del desarrollo

Sus antecedentes:

  • El desarrollo de metazoos se basa en la proliferación de células progenitoras regidas por redes de transcripción.
  • La expresión génica se detiene durante la mitosis, lo que requiere el reinicio de los programas de identidad celular en cada ciclo.
  • Los mecanismos para reiniciar estos programas de transcripción después de la mitosis no se comprenden bien.

Objetivo del estudio:

  • Identificar los mecanismos moleculares que reinician la expresión génica y mantienen la identidad celular después de la mitosis.
  • Aclarar el papel de las vías dependientes de la ubiquitina en la transcripción regulada por el ciclo celular.

Principales métodos:

  • Se investigó la interacción de WDR5 y TBP con los sitios de inicio de la transcripción durante la mitosis.
  • Se utilizaron ensayos bioquímicos para detectar la ubiquitinación de histonas y el reclutamiento de proteínas.
  • Se examinó el papel del complejo promotor de la anafase (APC/C) en la regulación de la expresión génica después de la mitosis.

Principales resultados:

  • Se identificaron WDR5 y TBP como factores que reclutan el complejo promotor de la anafase (APC/C) a los promotores durante la mitosis.
  • Se ha demostrado que APC/C ubiquitina las histonas con cadenas ramificadas K11/K48.
  • Se demostró que estas histonas ubiquitinadas reclutan p97 y el proteosoma para facilitar la rápida expresión del gen de pluripotencia en el ciclo celular posterior.

Conclusiones:

  • Un mecanismo dependiente de la ubiquitina que involucra a APC/C integra la expresión génica con la división celular para preservar la identidad celular.
  • APC/C actúa como un regulador clave que controla tanto la salida mitótica como el reinicio de la transcripción.
  • Esta vía proporciona un mecanismo robusto para mantener la identidad celular a través de las divisiones celulares.