Competition for cellular factors that activate metallothionein gene transcription

Metallothioneins (MTs), small cysteine-rich proteins, bind to and are inducible by heavy metals such as zinc, cadmium and copper. Recent gene-transfer and mutagenesis experiments have elucidated cis-acting DNA sequences involved in this form of regulation, but nothing is known about the trans-acting factors that interact with the control sequences or how such interactions influence the rate of transcription. We report here the detection of cellular factors involved in the cadmium induction of the mouse MT-1 gene by an in vivo competition assay. We show that at least one-class of these cellular factors acts by a positive regulatory mechanism depending on the same region of the 5' flanking DNA required for maximal transcription.