title: Two remote glucocorticoid responsive units interact cooperatively to promote glucocorticoid induction of rat tyrosine aminotransferase gene expression.
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.
authors.affiliation: Institut Jacques Monod du CNRS, Université Paris 7, France.
authors.forename: T
authors.initials: T
authors.lastname: Grange
authors.forename: J
authors.initials: J
authors.lastname: Roux
authors.forename: G
authors.initials: G
authors.lastname: Rigaud
authors.forename: R
authors.initials: R
authors.lastname: Pictet
mesh_terms: D000818:Animals; D001483:Base Sequence; D004256:DNA Polymerase I / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D008969:Molecular Sequence Data; D010957:Plasmids; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014444:Tyrosine Transaminase / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014444:Tyrosine Transaminase; D004256:DNA Polymerase I