Glucocorticoid-induced DNA demethylation and gene memory during development.
EMBO J
; 20(8): 1974-83, 2001 Apr 17.
Article
en En
| MEDLINE
| ID: mdl-11296230
Glucocorticoid hormones were found to regulate DNA demethylation within a key enhancer of the rat liver-specific tyrosine aminotransferase (Tat) gene. Genomic footprinting analysis shows that the glucocorticoid receptor uses local DNA demethylation as one of several steps to recruit transcription factors in hepatoma cells. Demethylation occurs within 2-3 days following rapid (< 1 h) chromatin remodeling and recruitment of a first transcription factor, HNF-3. Upon demethylation, two additional transcription factors are recruited when chromatin is remodeled. In contrast to chromatin remodeling, the demethylation is stable following hormone withdrawal. As a stronger subsequent glucocorticoid response is observed, demethylation appears to provide memory of the first stimulation. During development, this demethylation occurs before birth, at a stage where the Tat gene is not yet inducible, and it could thus prepare the enhancer for subsequent stimulation by hypoglycemia at birth. In vitro cultures of fetal hepatocytes recapitulate the regulation analyzed in hepatoma cells. There fore, demethylation appears to contribute to the fine-tuning of the enhancer and to the memorization of a regulatory event during development.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tirosina Transaminasa
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Dexametasona
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Cromatina
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Receptores de Glucocorticoides
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Regulación de la Expresión Génica
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Metilación de ADN
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Glucocorticoides
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Hígado
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2001
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido