The synthesis of the
glutathione S-transferase Ya subunit is induced in the mammalian liver by chemicals such as
phenobarbital and
3-methylcholanthrene. To study the mechanism of this induction, the 5'-flanking region of a mouse
glutathione S-transferase Ya subunit gene was fused to the structural gene for
chloramphenicol acetyltransferase. The fusion gene was introduced into
hepatoma cells for the assay of the expressed
acetyltransferase activity. At least two cis-regulatory elements were identified in the 5'-flanking region of the Ya gene: one, responsible for the basal level of expression, is present in the sequence up to -0.2 kb; another, responsible for the inducible expression by aromatic compounds such as
beta-naphthoflavone and
3-methylcholanthrene, is located in the sequence from -0.2 kb to -1.6 kb. The inducible
element was functional only in cells with normal aromatic compound receptors, and it retained responsiveness to
beta-naphthoflavone when transfected into homologous (mouse) or heterologous (rat, human)
hepatoma cells. A 150-bp region upstream from the transcription initiation site of the mouse Ya gene was investigated for cis-acting transcriptional elements that are recognized by specific
DNA-binding proteins. We show by
DNase I foot-printing assays using extracts from liver nuclei that the Ya gene promoter contains, in addition to the TATA and CCAAT boxes, a more distal
element that binds a
protein which is probably related to the family of
nuclear factor 1 (NF1).