The vitamin D response element of the involucrin gene mediates its regulation by 1,25-dihydroxyvitamin D3.
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.
Bikle
Daniel D
DD
Department of Medicine, Veterans Affairs Medical Center and University of California, San Francisco, USA. Doctor@itsa.ucsf.edu
Ng
Dean
D
Oda
Yuko
Y
Hanley
Karen
K
Feingold
Kenneth
K
Xie
Zhongjian
Z
D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements / Q000235:genetics*; D014162:Transfection
D002120:Calcium Channel Agonists; D011498:Protein Precursors; D012333:RNA, Messenger; C032253:involucrin; D002117:Calcitriol; D002118:Calcium