Overlapping but unique DNA binding specificities of the Ah receptor and constitutive dioxin-responsive element...

To understand the relationships between the protein architecture assembled on dioxin-responsive elements (DRE) and transcriptional regulation by dioxin in human keratinocytes, the nuclear DRE-binding proteins from human keratinocytes were identified and characterized. In addition to the aryl hydrocarbon receptor (AHR) complex inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), nuclear extracts from 3 human keratinocyte cell lines also contained one or more proteins that bound specifically to the DRE but whose levels were unaffected by TCDD or by anti-AHR antibody pretreatment. Alteration of a conserved T, within the core DRE sequence needed for transcriptional activation by the AHR complex, did not affect AHR binding but severely affected the ability of the constitutive proteins to bind. These data suggest that the nonidentical interplay of the AHR and constitutive DRE-binding proteins on the DRE is important in the regulation of genes whose expression is controlled by DRE.