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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.

A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene.

N Toyoda, A M Zavacki, A L Maia, J W Harney, P R Larsen
N Toyoda
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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A M Zavacki
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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A L Maia
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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J W Harney
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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P R Larsen
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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DOI: 10.1128/MCB.15.9.5100
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ABSTRACT

We identified two thyroid hormone response elements (TREs) in the 2.5-kb, 5'-flanking region of the human gene encoding type 1 iodothyronine deiodinase (hdio1), an enzyme which catalyses the activation of thyroxine to 3,5,3'-triiodothyronine (T3). Both TREs contribute equally to T3 induction of the homologous promoter in transient expression assays. The proximal TRE (TRE1), which is located at bp -100, has an unusual structure, a direct repeat of the octamer YYRGGTCA hexamer that is spaced by 10 bp. The pyrimidines in the -2 position relative to the core hexamer are both essential to function. In vitro binding studies of TRE1 showed no heterodimer formation with retinoid X receptor (RXR) beta or JEG nuclear extracts (containing RXR alpha) and bacterially expressed chicken T3 receptor alpha 1 (TR alpha) can occupy both half-sites although the 3' half-site is dominant. T3 causes dissociation of TR alpha from the 5' half-site but increases binding to the 3' half-site. Binding of a second TR to TRE1 is minimally cooperative; however, no cooperativity was noted for a functional mutant in which the half-sites are separated by 15 bp, implying that TRs bind as independent monomers. Nonetheless, T3 still causes TR dissociation from the DR+15, indicating that dissociation occurs independently of TR-TR contact and that rebinding of a T3-TR complex to the 3' half-site occurs because of its slightly higher affinity. A distal TRE (TRE2) is found at bp -700 and is a direct repeat of a PuGGTCA hexamer spaced by 4 bp. It has typical TR homodimer and TR-RXR heterodimer binding properties. The TRE1 of hdio1 is the first example of a naturally occurring TRE consisting of two relatively independent octamer sequences which do not require the RXR family of proteins for function.

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A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene.
N Toyoda, A M Zavacki, A L Maia, J W Harney, P R Larsen
Molecular and Cellular Biology Sep 1995, 15 (9) 5100-5112; DOI: 10.1128/MCB.15.9.5100

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A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene.
N Toyoda, A M Zavacki, A L Maia, J W Harney, P R Larsen
Molecular and Cellular Biology Sep 1995, 15 (9) 5100-5112; DOI: 10.1128/MCB.15.9.5100
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