Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors

Cell. 1991 Jun 28;65(7):1255-66. doi: 10.1016/0092-8674(91)90020-y.


We report here the identification of thyroid hormone response elements (TREs) that consist of a direct repeat, not a palindrome, of the half-sites. Unlike palindromic TREs, direct repeat TREs do not confer a retinoic acid response. The tandem TRE can be converted into a retinoic acid response element by increasing the spacing between the half-sites by 1 nucleotide, and the resulting retinoic acid response element is no longer a TRE. Decreasing the half-site spacing by 1 nucleotide converts the TRE to a vitamin D3 response element, while eliminating response to T3. These results correlate well with DNA-binding affinities of the thyroid hormone, retinoic acid, and vitamin D3 receptors. This study points to the general importance of tandem repeat hormone response elements and suggests a simple physiologic code exists in which half-site spacing plays a critical role in achieving selective hormonal response.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Calcitriol / physiology
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • In Vitro Techniques
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Rats
  • Receptors, Calcitriol
  • Receptors, Retinoic Acid
  • Receptors, Steroid / metabolism*
  • Receptors, Thyroid Hormone / metabolism*
  • Regulatory Sequences, Nucleic Acid*
  • Repetitive Sequences, Nucleic Acid
  • Structure-Activity Relationship
  • Tretinoin / metabolism


  • Carrier Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptors, Calcitriol
  • Receptors, Retinoic Acid
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Tretinoin
  • Calcitriol