1. The Vitamin D Response Element of the Involucrin Gene Mediates its Regulation by 1,25-Dihydroxyvitamin D3
- Author
-
Kenneth R. Feingold, Yuko Oda, Dean Ng, Karen Hanley, Zhongjian Xie, and Daniel D. Bikle
- Subjects
keratinocytes ,medicine.medical_specialty ,Gene Expression ,chemistry.chemical_element ,Dermatology ,δP-1 ,Retinoid X receptor ,Calcium ,Biology ,Response Elements ,Transfection ,Biochemistry ,Calcitriol receptor ,involucrin ,Cornified envelope ,Calcitriol ,Vitamin D Response Element ,Internal medicine ,medicine ,Humans ,vitamin D receptor ,DR3 ,RNA, Messenger ,Protein Precursors ,PBS ,PPARa ,Molecular Biology ,Involucrin ,Cells, Cultured ,integumentary system ,Drug Synergism ,Cell Biology ,AP-1 ,Cell biology ,Calcium Channel Agonists ,Retinoic acid receptor ,Endocrinology ,medicine.anatomical_structure ,chemistry ,LXR ,vitamin D response element ,Keratinocyte ,Gene Deletion - Abstract
Involucrin is a major protein of the cornified envelope of keratinocytes that provides much of the structural integrity of skin. Its expression is stimulated by a number of agents including calcium and 1,25-dihydroxy-vitamin D3 that promote the differentiation process in keratinocytes. Within the distal regulatory region of the involucrin promoter lies an AP-1 site and an element homologous to other vitamin D response elements. In previous studies mutation of the AP-1 site was found to reduce basal activity and block calcium stimulation of the involucrin promoter, whereas the vitamin D response element was not critical for calcium regulation. In this study both elements proved to be important for 1,25-dihydroxyvitamin D3 stimulation of the involucrin promoter. Mutation of the AP-1 site reduced basal activity and blocked 1,25-dihydroxyvitamin D3 stimulation of the involucrin promoter. In contrast, mutation of the vitamin D response element did not reduce basal expression of the involucrin promoter or prevent calcium stimulation of involucrin gene expression, but blocked 1,25-dihydroxyvitamin D3 stimulation. The vitamin D response element from the involucrin gene bound the vitamin D receptor and the retinoid X receptor, but not the retinoic acid receptor, in a specific manner. We conclude that the AP-1 site and the vitamin D response element in the involucrin promoter play important roles in mediating the action of 1,25-dihydroxyvitamin D3 on involucrin expression, but the vitamin D response element provides specificity for the 1,25-dihydroxyvitamin D3 response lacking at the AP-1 site.
- Published
- 2002