Thionein (apometallothionein) can modulate DNA binding and transcription activation by zinc finger containing factor Sp1.
A number of transcription factors contain so-called zinc finger domains for the interaction with their cognate DNA sequence. It has been shown that removal of the zinc ions complexed in these zinc fingers abrogates DNA binding and transcription activation. Therefore we wanted to test the hypothesis that the activity of transcription factors could be regulated by physiological chelators of zinc. A prominent candidate for such a chelator is the Cys-rich protein thionein (apometallothionein) that is inducible by heavy metal loads, and by other environmental stimuli. Here we show with DNA binding and in vitro transcription assays that thionein indeed can inactivate the zinc finger-containing Sp1 in a reversible manner. By contrast, transcription factor Oct-1, which binds DNA via a homeo-domain, i.e. a helix-turn-helix motif not involving zinc ions, is refractory to thionein action. We propose that modulation of intracellular thionein concentration is used for the coordinated regulation of a large subset of genes whose transcription depends on zinc finger proteins.
Zeng
J
J
Biochemisches Institut der Universität Zürich, Switzerland.
Heuchel
R
R
Schaffner
W
W
Kägi
J H
JH
D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008668:Metallothionein / Q000378:metabolism*; D011817:Rabbits; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism*
D001059:Apoproteins; D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D004247:DNA; D008668:Metallothionein; D015032:Zinc