title: The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements.
abstract: We report that the thyroid hormone (T3) receptor binds to DNA recognition sequences that are variations of the palindromic motif 5'-TCAGGTCA.TGACCTGA-3', resulting in transcriptional activation in vivo. This sequence is identical to the vitellogenin A2 estrogen response element except for the absence of 3 bp at the center of dyad symmetry, which we have termed a "gap." The T3 receptor binds to estrogen response elements with high affinity in vitro, as well as to variations of the same sequence containing gaps of 1-6 bp. The T3 receptor not only fails to activate transcription from estrogen response elements in vivo, but inhibits estrogen-dependent transactivation. We propose that the T3 receptor binds to estrogen response elements in a transcriptionally inactive form and competes for estrogen receptor binding, resulting in a net decrease in gene expression. These data reveal that only a subset of T3 receptor DNA-binding elements function as T3 response elements.
authors.affiliation: Eukaryotic Regulatory Biology Program, School of Medicine, University of California, San Diego, La Jolla 92093-0613.
authors.forename: C K
authors.initials: CK
authors.lastname: Glass
authors.forename: J M
authors.initials: JM
authors.lastname: Holloway
authors.forename: O V
authors.initials: OV
authors.lastname: Devary
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000235:genetics / Q000378:metabolism*; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism
chemical_list: D004967:Estrogens; D005938:Glucocorticoids; D011988:Receptors, Thyroid Hormone; D014819:Vitellogenins; D014284:Triiodothyronine; D011388:Prolactin; D004247:DNA