Nucleic Acids Research Advance Access originally published online on September 14, 2006
Nucleic Acids Research 2006 34(17):4866-4877; doi:10.1093/nar/gkl606
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Nucleic Acids Research, 2006, Vol. 34, No. 17 4866-4877
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Genomics |
Transcriptome response to heavy metal stress in Drosophila reveals a new zinc transporter that confers resistance to zinc
Institute of Molecular Biology, University of Zurich CH-8057 Zurich, Switzerland 1 Laboratory of Genetics, University of Wisconsin WI 53706-1580, USA 2 Freie Universität Berlin, Institut für Chemie und Biochemie D-14195 Berlin, Germany
*To whom correspondence should be addressed: Tel:+41 44 635 3150; Fax:+41 44 635 6811; Email: walter.schaffner{at}molbio.unizh.ch
Received April 28, 2006. Revised August 2, 2006. Accepted August 3, 2006.
All organisms are confronted with external variations in trace element abundance. To elucidate the mechanisms that maintain metal homeostasis and protect against heavy metal stress, we have determined the transcriptome responses in Drosophila to sublethal doses of cadmium, zinc, copper, as well as to copper depletion. Furthermore, we analyzed the transcriptome of a metal-responsive transcription factor (MTF-1) null mutant. The gene family encoding metallothioneins, and the ABC transporter CG10505 that encodes a homolog of ‘yeast cadmium factor’ were induced by all three metals. Zinc and cadmium responses have similar features: genes upregulated by both metals include those for glutathione S-transferases GstD2 and GstD5, and for zinc transporter-like proteins designated ZnT35C and ZnT63C. Several of the metal-induced genes that emerged in our study are regulated by the transcription factor MTF-1. mRNA studies in MTF-1 overexpressing or null mutant flies and in silico search for metal response elements (binding sites for MTF-1) confirmed novel MTF-1 regulated genes such as ferritins, the ABC transporter CG10505 and the zinc transporter ZnT35C. The latter was analyzed in most detail; biochemical and genetic approaches, including targeted mutation, indicate that ZnT35C is involved in cellular and organismal zinc efflux and plays a major role in zinc detoxification.
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