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Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome
Published on: March 2, 2018
La disminución de la transcripción de BDNF implica una fosforilación dependiente del calcio de MeCP2
Wen G Chen1, Qiang Chang, Yingxi Lin
1Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|November 1, 2003
Resumen
Las mutaciones en la proteína 2 de unión al metil-CpG (MeCP2) causan el síndrome de Rett. Este estudio muestra que MeCP2 reprime la expresión génica del BDNF en las neuronas, y su liberación tras la estimulación permite la activación génica, revelando su papel en la regulación génica dependiente de la actividad neuronal.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Genética La genética.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El síndrome de Rett es un trastorno del desarrollo neurológico causado por mutaciones en el gen MECP2.
- La proteína MeCP2 es un represor de la transcripción, pero su papel específico en las neuronas maduras no está claro.
Objetivo del estudio:
- Para investigar la función de MeCP2 en las neuronas postmitóticas.
- Para dilucidar el mecanismo de MeCP2 en la regulación de la expresión génica en respuesta a la actividad neuronal.
Principales métodos:
- Análisis de la unión de MeCP2 al promotor del gen BDNF.
- Investigando el efecto de la despolarización de la membrana en la unión de MeCP2 y la expresión de BDNF.
- Estudiar la fosforilación dependiente del calcio de MeCP2.
Principales resultados:
- MeCP2 se une selectivamente al promotor del BDNF III, reprimiendo su transcripción.
- La actividad neuronal (depolarización de la membrana) induce la fosforilación dependiente del calcio y la liberación de MeCP2.
- La liberación de MeCP2 facilita la transcripción del gen BDNF.
Conclusiones:
- MeCP2 es crucial para regular la expresión génica dependiente de la actividad neuronal.
- La desregulación del control genético mediado por MeCP2 puede contribuir a la patología del síndrome de Rett.
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