Functional AP1 and CRE response elements in the human keratinocyte transglutaminase promoter mediating Whn suppression

Expression of keratinocyte transglutaminase (TGM1) is critical for maturation of mammalian epidermis and occurs during squamous metaplasia. Examination of the TGM1 5'-flanking region in transient transfections of human epidermal cells revealed an AP1 site ≃ 1.5 kb upstream from the transcription start site and a CRE site ≃ 0.5 kb upstream that, combined, accounted for as much as 90% of the transcriptional activity. Upon incubation with nuclear extract, three electrophoretically separable protein complexes were formed by a CRE site oligonucleotide, one of which was competed by an AP1 response element. In super-shift analysis, c-Jun and JunD formed complexes with both the AP1 and CRE sequences. The AP1 and CRE sites were found to mediate the suppressive effects of the Whn transcription factor on the activity of the TGM1 promoter. Similarly, two previously described AP1 sites mediated Whn suppression of involucrin promoter activity. (C) 2000 Elsevier Science B.V.