Glucocorticoid-induced DNA demethylation and gene memory during development

被引:244
作者
Thomassin, H
Flavin, M
Espinás, ML
Grange, T
机构
[1] Univ Paris 06, CNRS, Inst Jacques Monod, F-75251 Paris 05, France
[2] Univ Paris 07, CNRS, Inst Jacques Monod, F-75251 Paris 05, France
关键词
chromatin; DNA methylation; liver; nuclear receptor; transcription;
D O I
10.1093/emboj/20.8.1974
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 tells. 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. Therefore, demethylation appears to contribute to the fine-tuning of the enhancer and to the memorization of a regulatory event during development.
引用
收藏
页码:1974 / 1983
页数:10
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