Identification of multiple metal regulatory elements in mouse metallothionein-I promoter by assaying synthetic sequences

Metallothionein genes are transcriptionally regulated by a number of inducers including heavy metals. Previous mutational analyses of the mouse metallothionein-I gene ( mMTI ) promoter have delineated a heavy-metal regulatory region between −60 and −42 relative to the transcription start site 1,2 ....

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Bibliographic Details
Published in:Nature (London) 1985-10, Vol.317 (6040), p.828-831
Main Authors: Stuart, Gary W, Searle, Peter F, Palmiter, Richard D
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological and medical sciences
Cell Line
Cricetinae
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation
Genes, Regulator
Humanities and Social Sciences
letter
Metallothionein - genetics
Metals - pharmacology
Mice
Molecular and cellular biology
Molecular genetics
multidisciplinary
Promoter Regions, Genetic
Science
Science (multidisciplinary)
Transcription, Genetic
Transfection
Zinc - pharmacology
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Summary:Metallothionein genes are transcriptionally regulated by a number of inducers including heavy metals. Previous mutational analyses of the mouse metallothionein-I gene ( mMTI ) promoter have delineated a heavy-metal regulatory region between −60 and −42 relative to the transcription start site 1,2 . A synthetic copy of a 12-base-pair (bp) conserved sequence located within this region was subsequently shown to confer heavy-metal regulation on a heterologous gene 1,3 . However, specific disruption of this metal regulatory element (MRE) within a wild-type mMTI promoter reduced but did not eliminate the heavy-metal response. The additional metal regulatory activity was localized to an upstream region containing four sequences homologous to the identified MRE 1 . Similar sequences were also found in multiple copies in metallothionein genes from other species. Here we test synthetic copies of all five mMTI MRE homologues for metal regulatory activity. At least four of these sequences are able to confer heavy-metal regulation on a heterologous promoter.
ISSN:0028-0836
1476-4687
DOI:10.1038/317828a0