This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garlatti, M Articles by Barouki, R Search for Related Content PubMed PubMed Citation Articles by Garlatti, M Articles by Barouki, R

A functional glucocorticoid-responsive unit composed of two overlapping inactive receptor-binding sites: evidence for formation of a receptor tetramer.

U-99 INSERM, Hôpital Henri Mondor, Créteil, France.

ABSTRACT

An unusual glucocorticoid-responsive element (called GRE A) was found to mediate the induction of the cytosolic aspartate aminotransferase gene by glucocorticoids and was bound by the glucocorticoid receptor in a DNase I footprinting assay. GRE A consists of two overlapping GREs, each comprising a conserved half-site and an imperfect half-site. The complete unit was able to confer glucocorticoid inducibility to a heterologous promoter (delta MTV-CAT). Mutation of any of the half-sites, including the imperfect ones, abolished inducibility by the hormone, demonstrating that each of the isolated GREs was inactive. In electrophoretic mobility shift assays, purified rat liver glucocorticoid receptor (GR) formed a low-mobility complex with GRE A, presumably containing a GR tetramer. When purified bacterially expressed DBD was used, low-mobility complexes as well as dimer and monomer complexes were formed. In inactive mutated oligonucleotides, no GR tetramer formation was detected. Modification of the imperfect half-sites in order to increase their affinity for GR gave a DNA sequence that bound a GR tetramer in a highly cooperative manner. This activated unit consisting of two overlapping consensus GREs mediated glucocorticoid induction with a higher efficiency than consensus GRE.

This article has been cited by other articles:

• Bromberg-White, J. L., Sen, E., Alam, S., Bodily, J. M., Meyers, C. (2003). Induction of the Upstream Regulatory Region of Human Papillomavirus Type 31 by Dexamethasone Is Differentiation Dependent. J. Virol. 77: 10975-10983 [Abstract] [Full Text]  
• Massaad, C., Houard, N., Lombès, M., Barouki, R. (1999). Modulation of Human Mineralocorticoid Receptor Function by Protein Kinase A. Mol. Endocrinol. 13: 57-65 [Abstract] [Full Text]  
• Massaad, C., Lombes, M., Aggerbeck, M., Rafestin-Oblin, M.-E., Barouki, R. (1997). Cell-Specific, Promoter-Dependent Mineralocorticoid Agonist Activity of Spironolactone. Mol. Pharmacol. 51: 285-292 [Abstract] [Full Text]  
• Garlatti, M., Aggerbeck, M., Bouguet, J., Barouki, R. (1996). Contribution of a Nuclear Factor 1Binding Site to the Glucocorticoid Regulation of the Cytosolic Aspartate Aminotransferase Gene Promoter. J. Biol. Chem. 271: 32629-32634 [Abstract] [Full Text]  
• Massaad, C., Paradon, M., Jacques, C., Salvat, C., Bereziat, G., Berenbaum, F., Olivier, J.-L. (2000). Induction of Secreted Type IIA Phospholipase A2 Gene Transcription by Interleukin-1beta . ROLE OF C/EBP FACTORS. J. Biol. Chem. 275: 22686-22694 [Abstract] [Full Text]