trans repression of the human metallothionein IIA gene promoter by PZ120, a novel 120-kilodalton zinc finger protein

Metallothioneins are small, highly conserved, cysteine-rich proteins that b ind a variety of metal ions. They are found in virtually all eukaryotic org anisms and are regulated primarily at the transcriptional level. In humans, the predominant metallothionein gene is hMTIIA, which accounts for 50% of all metallothioneins expressed in cultured human cells. The hMTIIA promoter is quite complex. In addition to cis-acting DNA sequences that serve as bi nding sites for trans-acting factors such as Spl, AP1, AP2, AP4, and the gl ucocorticoid receptor, the hMTIIA promoter contains eight consensus metal r esponse element sequences. We report here the cloning of a novel zinc finge r protein with a molecular mass of 120 kDa (PZ120) that interacts specifica lly with the hMTIIA transcription initiation site. The PZ120 protein is ubi quitously expressed in most tissues and possesses a conserved poxvirus and zinc finger (POZ) motif previously found in several zinc finger transcripti on factors. Intriguingly, we found that a region of PZ120 outside of the zi nc finger domain can bind specifically to the hMTIIA DNA. Using transient-t ransfection analysis, we found that PZ120 repressed transcription of the hM TIIA promoter. These results suggest that the hMTIIA gene is regulated by a n additional negative regulator that has not been previously described.