Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes.
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.
Selvaraj
Anand
A
Institute of Molecular Biology, University of Zurich, CH-8057, Zurich, Switzerland.
Balamurugan
Kuppusamy
K
Yepiskoposyan
Hasmik
H
Zhou
Hao
H
Egli
Dieter
D
Georgiev
Oleg
O
Thiele
Dennis J
DJ
Schaffner
Walter
W
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D027682:Cation Transport Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019295:Computational Biology; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D040461:Gene Components; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D017136:Ion Transport / Q000502:physiology; D008668:Metallothionein / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D000097809:Transcription Factor MTF-1
D027682:Cation Transport Proteins; D003300:Copper; D000079923:Copper Transporter 1; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D008668:Metallothionein; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1; C485184:enhanced green fluorescent protein