Original MRE-binding transcriptional factor gene in normal humans is ZRF, not MTF-1

Metallothionein gene is transcriptionally regulated by heavy metals through cis-acting metal responsive elements (MREs). Two proteins, metal-regulatory transcription factor-1 (MTF-1) and zinc regulatory factor (ZRF), have been isolated and cloned from human cells as MRE-binding transcriptional factor (MREBT). These proteins are almost identical to each other, except for only one base substitution at codon 185 that causes an amino acid change from histidine to tyrosine. This single amino acid difference has been reported to influence zinc-responsive transcriptional activities. In this study, we determined the nucleotide sequence of the region containing codon 185 in DNA samples obtained from normal Japanese (n = 30) and three human-derived cultured cell lines. The findings indicate that all subjects have the same sequence identical to ZRF, suggesting that ZRF is the original MREBT gene in normal humans, and MTF-1 is its minor variant.