Abstract:
:Synthesis of mouse metallothionein (MT)-I and MT-II is transcriptionally induced by the synthetic glucocorticoid, dexamethasone (DEX) or both in vivo as well as in numerous cell lines. However, the location(s) of a glucocorticoid response element (GRE) has not been described. The observation that a marked MT-I gene, as well as heterologous genes, when placed in the context of 17 kb of flanking sequence from the MT locus, are inducible by DEX and lipopolysaccharide in transgenic mice renewed the search for the GRE. Analysis of a series of deletion constructs from this 17-kb region in cultured cells identified a single 455-bp region that conferred DEX induction on a reporter gene. This 455-bp region contains two GREs that bind to the glucocorticoid receptor as assessed by gel mobility shift. Deletion of this fragment from the 17-kb flanking region eliminates the DEX responsiveness of reporter genes. The two GREs, which are located approximately 1 kb upstream of the MT-II gene and approximately 7 kb upstream of the MT-I gene, are necessary for induction of both genes and can function independently of elements within the proximal promoter region of either gene.
journal_name
Proc Natl Acad Sci U S Aauthors
Kelly EJ,Sandgren EP,Brinster RL,Palmiter RDdoi
10.1073/pnas.94.19.10045subject
Has Abstractpub_date
1997-09-16 00:00:00pages
10045-50issue
19eissn
0027-8424issn
1091-6490journal_volume
94pub_type
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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