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Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
Published on: August 13, 2013
Un silenciador transcripcional específico del linaje regula la expresión del gen CD4 durante el desarrollo de los
S Sawada1, J D Scarborough, N Killeen
1Department of Microbiology and Immunology, University of California, San Francisco 94143-0414.
Cell
|June 17, 1994
Resumen
Los investigadores identificaron una región reguladora del ADN que controla la expresión del gen CD4 en las células T en desarrollo. Este elemento silenciador es crucial para dirigir la diferenciación de las células T en linajes auxiliares o citotóxicos.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del desarrollo Biología del desarrollo.
- Genética molecular La genética molecular.
Sus antecedentes:
- La diferenciación de los linfocitos T implica la expresión diferencial de los coreceptores CD4 y CD8.
- El compromiso con los linajes auxiliares o citotóxicos requiere el silenciamiento selectivo de CD4 o CD8.
- Comprender los mecanismos reguladores que rigen la expresión de CD4 y CD8 es fundamental para el desarrollo de las células T.
Objetivo del estudio:
- Identificar los elementos reguladores que controlan la expresión del gen CD4 durante el desarrollo de los linfocitos T.
- Para caracterizar la función y las propiedades de una nueva región reguladora dentro del locus del gen CD4.
- Para investigar el papel de esta región en el compromiso del linaje de células T.
Principales métodos:
- Utilizó modelos de ratón transgénicos para estudiar la regulación génica.
- Se analizaron los patrones de expresión de un transgen controlado por la región reguladora identificada.
- Se evaluó el impacto de la región reguladora en la expresión génica en diferentes subconjuntos de timocitos.
Principales resultados:
- Se identificó una región reguladora intrónica que reprime selectivamente la expresión del transgen CD4 en los timocitos CD4-CD8+.
- Se demostró que esta región también reprime la expresión en los timocitos CD4-CD8 inmaduros.
- Se demostró que el elemento regulador funciona independientemente de la orientación y la posición, y puede actuar sobre secuencias heterólogas.
- Caracterizó el elemento como un potente silenciador transcripcional con propiedades similares a las de la levadura y los silenciadores de Drosophila.
Conclusiones:
- El gen CD4 se desreprime durante la diferenciación de los timocitos CD4-CD8 a CD4+CD8+.
- Un nuevo silenciador transcripcional de vertebrados regulado por el desarrollo controla la expresión de CD4.
- Este silenciador juega un papel clave en el compromiso del linaje de células T mediante la regulación de la expresión de CD4.
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