JUN-RELATED AND FOS-RELATED GENE-PRODUCTS BIND TO AND MODULATE THE GPE-I, A STRONG ENHANCER ELEMENT OF THE RAT GLUTATHIONE TRANSFERASE-P GENE

The rat glutathione transferase P gene has a strong enhancer element, termed GPE I, which is composed of a dyad of palindromically oriented TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive element (TRE)- like sequences. TRE is a binding sequence of the transcription factor AP-1, which consists of several closely related proteins belonging to the Jun and Fos family. The gel retardation experiments show that all the heterodimers formed between the Jun and Fos related gene products bind to the GPE I as well as to the TRE. In spite of the fact that the GPE I has a stronger activity than the TRE, the binding affinities of these heterodimers to the GPE I are much lower than to the TRE. Co-tr ansfection studies of the reporter construct containing the GPE I and expression constructs of each of the Jun and Fos family cDNAs indicate that FosB and Delta FosB repress transcription through the GPE I enha ncer. These results suggests that some of Jun/Fos family may regulate the rat GST-P gene expression through the GPE I in vivo.