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MTF-1 is absolutely essential for upregulation of MT-I gene expression in visceral endoderm cells and that optimal expression also involves interactions of the basic helix-loop-helix upstream stimulatory factor-1 (USF1) with an E-box1-containing sequence at -223 bp in the MT-I promoter. Metal ion regulation of MT expression is mediated by metal response elements (MREs). MRE-binding transcription factor-1 (MTF-1), a six zinc-finger protein of the Cys2His2 family, binds directly and specifically to MREs (Westin and Schaffner, 1988; Radtke et al., 1993; Koizumi et al., 1999) and regulates metal-induced and basal MT expression in cultured cells (Heuchel et al., 1994).
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