The vitamin D response element of the involucrin gene mediates its regulation by 1,25-dihydroxyvitamin D3

J Invest Dermatol. 2002 Nov;119(5):1109-13. doi: 10.1046/j.1523-1747.2002.19508.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Calcitriol / pharmacology*
  • Calcium / pharmacology
  • Calcium Channel Agonists / pharmacology*
  • Cells, Cultured
  • Drug Synergism
  • Gene Deletion
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / physiology*
  • Protein Precursors / genetics*
  • RNA, Messenger / metabolism
  • Response Elements / genetics*
  • Transfection


  • Calcium Channel Agonists
  • Protein Precursors
  • RNA, Messenger
  • involucrin
  • Calcitriol
  • Calcium