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PMID: 3582368 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid-responsive elements.

The EMBO journal ·Vol. 6 ·No. 3 ·1987-03-00 ·Pages 625-30

Danesch U, Gloss B, Schmid W, Schütz G, Schüle R, Renkawitz R

Abstract

Transcription of the gene coding for tryptophan oxygenase (TO) in rat liver is induced 10-fold by glucocorticoids. To identify DNA elements mediating the glucocorticoid-regulated expression of the TO gene we transfected mouse L cells with a fusion gene consisting of 1.95 kb TO 5'-flanking sequences linked to the coding sequence of the gene for chloramphenicol acetyltransferase (CAT). CAT assay and RNA mapping experiments demonstrate that both transient and stable expression of the TO-CAT fusion gene are inducible by dexamethasone. Analysis of transcripts from 5'-deletion mutants identifies two glucocorticoid-responsive elements (GRE), located 450 bp and 1.2 kb upstream of the cap site. The purified rat glucocorticoid receptor binds to the sequence of each GRE as evidenced from footprinting experiments. Interestingly the protected sequence of the proximal footprint is by itself not sufficient for sequence induction, but requires sequences located immediately upstream.

MeSH Terms
Adrenalectomy Animals Base Sequence Chromosome Deletion Cloning, Molecular DNA/isolation & purification Dexamethasone/pharmacology Enzyme Induction Female Genes/drug effects L Cells/enzymology Mice Mutation Rats Receptors, Glucocorticoid/isolation & purification,metabolism Transcription, Genetic Tryptophan Oxygenase/biosynthesis,genetics
Chemicals
Receptors, Glucocorticoid Dexamethasone DNA Tryptophan Oxygenase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Danesch U
Gloss B
Schmid W
Schütz G
Schüle R
Renkawitz R
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42 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1987-03-00
Pages
625-30
Language
English
Region
England
NLM ID
8208664
PMCID
PMC553443
Subset
IM
Databases
GENBANK
X05145
External Links
PubMed source PMC Full Text View journal details
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