Thyroid Hormone Response Elements



General

Thyroid hormone response elements are DNA sequences that bind thyroid hormone receptors and cause nearby genes to respond transcriptionally to thryroid hormone. Such responses are generally inductive, though there are several cases where increasing hormone levels decrease transcription. T3 response elements have been referred to as both TREs and T3REs. Since the former term can lead to confusion with AP-1 sites, which are sometimes called TPA response elements (TREs), T3REs will be used here.

Thyroid hormone response elements are built from one or more copies of a sequence that matches a consensus motif: 5' AGGTCA 3.' All naturally occurring positive response elements identified to date include at least two copies of this motif, frequently arranged as a direct or head-to-tail repeat separated by 4 base pairs. Such sites are referred to as DR-4 elements. Elements that include head-to-head repeats (eg. AGGTCATGACCT) are called palindromes or inverted repeats (thus, IR-0 for the preceding element that has no base pairs separating the hexamers). Those with tail-to-tail repeats are called everted repeats (eg. ER-6 = TGACCTNNNNNNAGGTCA). Naturally occurring T3REs of the ER-6 type are also relatively common. Elements of the IR-0 type seem less common, but synthetic versions of such sites confer potent T3 responses. Positive response is also associated with T3REs that match an octameric monomer binding consensus, TAAGGTCA, but no naturally occuring examples of such elements have yet been identified.

Positive Elements, Negative Elements



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