Specificity and mechanism of thyroid hormone induction from an octamer response element

• Published in: The Journal of biological chemistry Vol. 269; no. 29; pp. 18915 - 18920
• Main Authors: KATZ, R. W, KOENIG, R. J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 22.07.1994
• Subjects: Animals; Base Sequence; Binding Sites; Biological and medical sciences; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; Protein Binding; Rats; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Retinoic Acid; Receptors, Thyroid Hormone - metabolism; Recombinant Proteins; Regulatory Sequences, Nucleic Acid; Retinoid X Receptors; Transcription Factors; Transcription. Transcription factor. Splicing. Rna processing; Site specificity; Ligand binding; Transcription; Nucleotide sequence; Transcription promoter; Thyroid hormone; Regulatory sequence; Gel retardation technique; Hormonal receptor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)32254-8

Thyroid hormone response elements are specific DNA sequences that allow thyroid hormone receptors to confer ligand-dependent regulation of gene expression. The response elements characterized to date have been composed of varying arrangements of multiple copies of a conserved hexameric sequence. The traditional consensus half-site of these response elements is the sequence 5'-AGGTCA, although we have demonstrated recently that the optimal thyroid hormone receptor monomer binding site is 2 base pairs larger, 5'-TAAGGTCA. Since other members of this family of nuclear receptors also have been shown to use varying arrangements of the traditional hexamer sequence as response elements, we examined whether the octamer sequence was specific as a thyroid hormone response element. The studies reported here demonstrate that only thyroid hormone receptors confer ligand responsiveness to a reporter gene containing a single copy of the octamer sequence as a response element and that qualitative and quantitative differences in the binding of related nuclear receptors to this sequence can account for this functional specificity. We also have shown that thyroid hormone induction from the octamer response element occurs independently of retinoid X receptors, in contrast to the induction from traditional complex thyroid hormone response elements.