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RESEARCH COMMUNICATION
1 Institute of Molecular Biology, University of Zurich, CH-8057, Zurich, Switzerland; 2 Howard Hughes Medical Institute, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA; 3 Department of Pharmacology and Cancer Biology, Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27710, USA
From insects to mammals, metallothionein genes are induced in response to heavy metal load by the transcription factor MTF-1, which binds to short DNA sequence motifs, termed metal response elements (MREs). Here we describe a novel and seemingly paradoxical role for MTF-1 in Drosophila in that it also mediates transcriptional activation of Ctr1B, a copper importer, upon copper depletion. Activation depends on the same type of MRE motifs in the upstream region of the Ctr1B gene as are normally required for metal induction. Thus, a single transcription factor, MTF-1, plays a direct role in both copper detoxification and acquisition by inducing the expression of metallothioneins and of a copper importer, respectively.
[Keywords: Transcription factor MTF-1; metal response elements; metallothioneins; Ctr1B; copper load; copper depletion]
Received January 31, 2005; revised version accepted March 4, 2005.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1301805.
4 These authors contributed equally to this work.
5 Corresponding author.
E-MAIL walter.schaffner{at}molbio.unizh.ch; FAX 41-1-6356811.
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