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. 1989 Nov 11;17(21):8695–8709. doi: 10.1093/nar/17.21.8695

Two remote glucocorticoid responsive units interact cooperatively to promote glucocorticoid induction of rat tyrosine aminotransferase gene expression.

T Grange 1, J Roux 1, G Rigaud 1, R Pictet 1
PMCID: PMC335037  PMID: 2573877

Abstract

Tyrosine aminotransferase (TAT) gene transcription is specifically activated by glucocorticoid hormones in liver cells. This regulation involves a glucocorticoid responsive region located 2,500 bases upstream from the transcription start site of the rate gene. By transient transfection of TAT-CAT fusion genes into a rat hepatoma cell line expressing the TAT gene we found that this region promotes only 30% of the glucocorticoid stimulation. We have identified a new cis-acting region far upstream (-5,400) from the transcription start site that is essential to achieve the physiological level of glucocorticoid stimulation of endogenous TAT gene expression. This region corresponds to a tissue-specific DNAse I hypersensitive site which is constitutive despite the fact it possesses a glucocorticoid receptor binding site. It is by itself almost inactive on a promoter but it cooperatively enhances the action of the proximal glucocorticoid responsive region. Its activity requires both the glucocorticoid receptor binding site and its flanking sequences.

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Selected References

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