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Publication : Analysis of the heavy metal-responsive transcription factor MTF-1 from human and mouse.

First Author  Müller HP Year  1995
Journal  Somat Cell Mol Genet Volume  21
Issue  5 Pages  289-97
PubMed ID  8619126 Mgi Jnum  J:32168
Mgi Id  MGI:79673 Doi  10.1007/BF02257464
Citation  Muller HP, et al. (1995) Analysis of the heavy metal-responsive transcription factor MTF-1 from human and mouse. Somat Cell Mol Genet 21(5):289-97
abstractText  Heavy metal-induced transcription in mammalian cells is conferred by the metal-responsive 70 kDa transcription factor MTF-1 which contains six zinc fingers and at least three activation domains. In previous cell transfection experiments we have shown that the zinc finger region confers an about 3 fold metal inducibility of transcription, due to its differential zinc binding. However, we also noted that human MTF-1 was more metal-responsive than the mouse factor (about 10 fold versus 3 fold, respectively). Here we analyze this difference in more detail by using chimeric human-mouse factors and narrow the critical region to a 64 amino acid stretch immediately downstream of the zinc fingers, overlapping with the acidic activation domain. A short human segment of this region (aa 313-377) confers efficient metal induction to the mouse MTF-1 when replacing the corresponding mouse region. However, high metal inducibility requires an unaltered MTF-1 and is lost when human MTF-1 is fused to the general activation domain of herpesvirus VP16. Wild type and truncation mutants of MTF-1 fused to VP16 yield chimeras of high transcriptional activity, some exceeding the wildtype regulator, but only limited (about 3 fold) heavy metal inducibility.
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