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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Circadian Rhythms and Gene Regulation02:19

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Prokaryotic Transcriptional Activators and Repressors01:58

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Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter
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Se requiere un retraso en la represión de retroalimentación por el criptocromo 1 para la función del reloj

Maki Ukai-Tadenuma1, Rikuhiro G Yamada, Haiyan Xu

  • 1Laboratory for Systems Biology, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Hyogo, Japan.

Cell
|January 18, 2011
PubMed
Resumen

Retrasar la expresión del criptocromo 1 (Cry1) es crucial para que el reloj circadiano de los mamíferos funcione correctamente. Esta investigación demuestra cómo elementos específicos del ADN controlan el Cry1.

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Área de la Ciencia:

  • Cronobiología cronobiología.
  • Biología Molecular Biología Molecular
  • Genética La genética.

Sus antecedentes:

  • El reloj circadiano de los mamíferos regula los ritmos biológicos diarios.
  • La represión de la retroalimentación es esencial para la función del reloj, pero ha faltado evidencia directa.
  • El criptocromo 1 (Cry1) es una proteína clave involucrada en la regulación del ritmo circadiano.

Objetivo del estudio:

  • Para investigar el requisito de la represión de retroalimentación retardada en el reloj circadiano de los mamíferos.
  • Aclarar los mecanismos reguladores que subyacen a la expresión nocturna del criptocromo 1 (Cry1).
  • Determinar el papel del tiempo de expresión de Cry1 en el mantenimiento de la ritmicidad circadiana.

Principales métodos:

  • Análisis de los elementos reguladores del gen Cry1, incluidas las cajas D y las RRE.
  • Construcción y prueba de un promotor de compuesto sintético para Cry1.
  • Desarrollo y aplicación de un modelo de vector de fase.
  • Ensayos de complementación genética en las células Cry1(-/-):Cry2(-/-.

Principales resultados:

  • Una combinación de elementos diurnos (caja D) y nocturnos (RREs) impulsa la expresión Cry1 nocturna.
  • Un promotor sintético recapituló este patrón de expresión.
  • Se observó la modulación del retraso de fase mediante la coordinación de estos elementos.
  • El retraso sustancial en la expresión de Cry1 fue necesario para restaurar la ritmicidad circadiana en las células knockout.
  • El retraso prolongado de Cry1 condujo a una desaceleración de las oscilaciones circadianas.

Conclusiones:

  • El retraso de fase en la transcripción del criptocromo 1 (Cry1) es un requisito crítico para la función del reloj de los mamíferos.
  • La interacción entre los elementos promotores y potenciadores dicta el tiempo de expresión de Cry1.
  • El tiempo preciso de la expresión de Cry1 influye en la velocidad de las oscilaciones circadianas.