Transition metals modulate DNA-protein interactions of SP1 zinc finger domains with its cognate target site.

The metal free apoprotein of recombinant human transcription factor SP1 was used in metal reconstitution experiments to study the importance of zinc in facilitating DNA binding of zinc finger proteins. Our functional analysis indicates that several transition metals are capable of modulating DNA-protein interactions of zinc finger domains with their cognate DNA target sites. Excess or deficiency of divalent zinc, or the presence of transition metals, such as divalent cadmium, cobalt, copper, manganese and nickel impair DNA binding of zinc reconstituted SP1. In addition, functionally active SP1 protein can be obtained by metal reconstitutions in absence of zinc(II) by presence of cadmium(II)- and cobalt(II)-, to lesser extents by presence of nickel(II)- or manganese(II)chloride. This study indicates that zinc might play a functional role in regulating DNA protein interactions of zinc finger proteins in vivo. It is postulated that fluctuating divalent zinc alone or transition metals bound to cellular components might form mixed-ligand complexes that alter the zinc finger protein conformation and impair DNA binding.