A ‘Swinging Cradle’ model for in vitro classification of different types of response elements of a nuclear receptor

• Published in: Biochemical and biophysical research communications 2005-11, Vol.337 (2), p.490-497
• Main Authors: Malo, Madhu S., Pushpakaran, Premraj, Hodin, Richard A.
• Format: Article
• Language: English
• Subjects: 3–4–5 rule; 60 APPLIED LIFE SCIENCES; Base Sequence; Binding site; Binding Sites; CRYSTAL STRUCTURE; Electrophoretic mobility shift assay; IN VITRO; Models, Biological; Molecular Sequence Data; Nuclear receptor; NUCLEOTIDES; Plasmids - genetics; Promoter; RECEPTORS; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Retinoic Acid - chemistry; Receptors, Retinoic Acid - metabolism; Receptors, Thyroid Hormone - metabolism; Response Elements; RETINOIC ACID; Thyroid hormone; THYROID HORMONES; TRANSCRIPTION FACTORS; Transcription, Genetic; VITAMIN D
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.09.080

Nuclear receptors are hormone-activated transcription factors that bind to specific target sequences termed hormone-response element (HRE). A HRE usually consists of two half-sites (5′-AGGTCA-3′ consensus sequence) arranged as a direct, everted or inverted repeat with variable spacer region. Assignment of a HRE as a direct, everted or inverted repeat is based on its homology to the consensus half-site, but minor variations can make such an assignment confusing. We hypothesize a ‘Swinging Cradle’ model for HRE classification, whereby the core HRE functions as the “sitting platform” for the NR, and the extra nucleotides at either end act as the “sling” of the Cradle. We show that in vitro binding of the thyroid hormone receptor and 9- cis retinoic acid receptor heterodimer to an everted repeat TRE follows the ‘Swinging Cradle’ model, whereas the other TREs do not. We also show that among these TREs, the everted repeat mediates the highest biological activity.