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Título

Glucocorticoid-induced DNA demethylation and gene memory during development

AutorThomassin, Hélène; Flavin, Michèle; Espinàs, Maria Lluïsa ; Grange, Thierry
Palabras claveChromatin
DNA methylation
Liver
Nuclear receptor
Transcription
Fecha de publicación17-abr-2001
EditorNature Publishing Group
CitaciónEMBO Journal 20(8): 1974–1983 (2001)
ResumenGlucocorticoid 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.
Descripción10 pages, 6 figures.-- PMID: 11296230 [PubMed].-- PMCID: PMC125428.
Versión del editorhttp://dx.doi.org/10.1093/emboj/20.8.1974
URIhttp://hdl.handle.net/10261/26446
DOI10.1093/emboj/20.8.1974
ISSN0261-4189 (Print)
1460-2075 (Online)
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