title: Efficient metal-specific transcription activation by Drosophila MTF-1 requires conserved cysteine residues in the carboxy-terminal domain.
abstract: MTF-1 is a sequence-specific DNA binding protein that activates the transcription of metal responsive genes. The extent of activation is dependent on the nature of the metal challenge. Here we identify separate regions within the Drosophila MTF-1 (dMTF-1) protein that are required for efficient copper- versus cadmium-induced transcription. dMTF-1 contains a number of potential metal binding regions that might allow metal discrimination including a DNA binding domain containing six zinc fingers and a highly conserved cysteine-rich C-terminus. We find that four of the zinc fingers in the DNA binding domain are essential for function but the DNA binding domain does not contribute to the metal discrimination by dMTF-1. We find that the conserved C-terminus of the cysteine-rich domain provides cadmium specificity while copper specificity maps to the previously described copper-binding region (Chen et al.). In addition, both metal specific domains are autorepressive in the absence of metal and contribute to the low level of basal transcription from metal inducible promoters.
authors.affiliation: Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Marr
authors.forename: Katie L
authors.initials: KL
authors.lastname: Pennington
authors.forename: Michael T
authors.initials: MT
authors.lastname: Marr
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004331:Drosophila melanogaster; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D016335:Zinc Fingers; D000097809:Transcription Factor MTF-1
chemical_list: D002104:Cadmium; D003300:Copper; D003545:Cysteine; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1