Radtke F Georgiev O Müller HP Brugnera E Schaffner W 1995 Metallothioneins (MTs) constitute a class of low molecular weight, cysteine-rich, metal binding proteins which are regulated at the level of gene transcription in response to heavy metals and other adverse treatments. We have previously cloned a zinc finger factor (MTF-1) that binds specifically to heavy metal-responsive DNA sequence elements in metallothionein promoters and shown that this factor is essential for basal and heavy metal-induced transcription. Here we report that the C-terminal part of MTF-1 downstream of the DNA binding zinc fingers harbours three different transactivation domains, namely an acidic domain, a proline-rich domain and a domain rich in serine and threonine. When fused to the heterologous DNA binding domain of the yeast factor GAL4 these activation domains function constitutively, i.e. transcription of a GAL4-driven reporter gene is not induced by heavy metals. In search of the region(s) responsible for metal induction, external and internal deletion mutations of mouse and human MTF-1 and chimeric variants thereof were tested with a reporter gene driven by a metal-responsive promoter. The N-terminal part of MTF-1 containing the zinc fingers, which are dependent on zinc for efficient DNA binding, can indeed confer a limited (3- to 4-fold) zinc-responsive transcription when fused to the heterologous activation domain of the viral VP16 protein. Another region containing the acidic and proline-rich activation domains also contributes to metal inducibility, but only in the context of intact MTF-1. This indicates that the activity of MTF-1 results from a complex interplay of different functional domains. https://sonar.ch/global/documents/118473 eng info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/23.12.2277 info:eu-repo/semantics/altIdentifier/pmid/7610056 Nucleic acids research. - 1995 Base Sequence Binding Sites DNA DNA-Binding Proteins Fungal Proteins Gene Deletion HeLa Cells Herpes Simplex Virus Protein Vmw65 Humans Hydrogen-Ion Concentration Metallothionein Metals Molecular Sequence Data Mutagenesis Plasmids Proline Promoter Regions, Genetic Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Serine Threonine Transcription Factors Transcriptional Activation Zinc Fingers Functional domains of the heavy metal-responsive transcription regulator MTF-1. http://purl.org/coar/resource_type/c_6501