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Nucleic Acids Research, 1989, Vol. 17, No. 21 8695-8709
© 1989

MOLECULAR BIOLOGY

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

Thierry Grange, Jeanne Roux, Gildas Rigaud and Raymond Pictet

Institut Jacques Monod du CNRS, Unité INSERM 257, Université Paris 7, Tour 43, 2 place Jussieu, 75251 Paris CEDEX 05, France

Received September 4, 1989. Accepted October 10, 1989.

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 rat 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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