Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.
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.
Umesono
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Gene Expression Laboratory, Howard Hughes Medical Institute, Salk Institute for Biological Studies, San Diego, California 92186-5800.
Murakami
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Thompson
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Evans
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002117:Calcitriol / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014212:Tretinoin; D002117:Calcitriol