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Metallothionein Gene Regulation in Mouse Cells

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Metal Ions in Gene Regulation

Part of the book series: Chapman & Hall Microbiology Series ((CHMBS))

Abstract

Heavy metals (Cd, Cu, Zn, etc.) can affect the expression of many genes. The best-known proteins that bind these metal ions are the metallothioneins (MTs). The genes encoding MTs are inducible at the transcriptional level by the same metal ions that the MTs bind. Metal activation of MT gene transcription is dependent on the presence of cis-acting DNA elements termed Metal Response Elements (MREs), and involves trans-acting protein (factor(s) interacting with the MREs, present in six nonidentical copies (MREa through MREf) in the 5′ flanking region of the mouse MT-I gene. Different MREs have different transcriptional efficiencies, MREd being the strongest. In vitro, footprinting analyses have revealed that one or more nuclear factors can bind to the different MRE elements of the mouse MT-1 gene. Moreover, the MREd binding activity is inactivated by EDTA and can be restored by addition of Zn2+. Using a Southwestern procedure, we found that a nuclear protein of 108 kDa, termed MEP-1, specifically binds to the different MRE elements of the mouse MT-I gene promoter. MEP-1 has been purified, and footprinting studies demonstrated that purified MEP-1 specifically binds to MRE sequences. MEP-1 binding activity is also inhibited by EDTA and can be restored by Zn2+.

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Authors
  1. Simon Labbé
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  2. Carl Simard
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  3. Carl Séguin
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Editors and Affiliations

  1. Department of Microbiology and Immunology, University of Illinois College of Medicine, M/C 790, Room 703 835 South Wolcott Avenue, Chicago, Illinois, 60612-7344, USA

    Simon Silver  & William Walden  & 

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© 1998 Springer Science+Business Media Dordrecht

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Labbé, S., Simard, C., Séguin, C. (1998). Metallothionein Gene Regulation in Mouse Cells. In: Silver, S., Walden, W. (eds) Metal Ions in Gene Regulation. Chapman & Hall Microbiology Series. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5993-1_9

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  • DOI: https://doi.org/10.1007/978-1-4615-5993-1_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7745-0

  • Online ISBN: 978-1-4615-5993-1

  • eBook Packages: Springer Book Archive

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