The metal response element (MRE)-binding transcription factor-1, MTF-1, is a zinc-responsive protein that controls transcription of metallothionein (MT) genes in many cell types. In addition, MTF-1 is also hypothesized to regulate transcription of a battery of genes involved in the defense against oxidative stress. Manipulating the Zn concentration in the low mu M range reversibly modulates the DNA-binding activity of the mammalian MTF-1; this effect is inhibited at low temperature. This report examines the presence and binding properties of MTF-1 in cell lines derived from warm- and cold-water fishes (zebrafish and trout, respectively). We found that both species of fish express MRE-specific binding activities that are immunologically similar to mouse MTF-1. MTF-1-binding from the cells of both species of fish was activated when cells were treated with Zn but not with Cd. Zebrafish cells contained a single isoform of MTF-1 with binding properties similar to mammalian MTF-1. Trout cells, on the other hand, contained two isoforms of MTF-1: MTF-1H and MTF-1L. Zn reversibly modulated MTF-1H binding in a temperature-dependent manner. Similarly, Zn reversibly modulated MTF-1L binding, but, in contrast, such modulation occurred readily at 4 degrees C. This data demonstrate the conservation of binding specificity, binding properties, and regulation of MTF-1 in fishes. (C) 2000 Elsevier Science Inc. All lights reserved.