Thyroid hormone receptor response elements

Miyamoto, T, Kaneko, A., Kakizawa, T, Yajima, H., Kamijo, K., Sekine, R., Hiramatsu, K., Nishii, Y, Hashimoto, T. Hashizume, K. (1997) Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element. J. biol. Chem., Ill, 7752-7758... 

Fig. 7. Model for activation by coactivators (A) and inhibition by corepressors (B) of transcription. Abbreviations CBP/p300, cAMP response element binding protein SRC-1, steroid receptor coactivator 1 TBP, TATA-binding protein TAF, TBP-associated factor pol II, RNA polymerase II N-CoR, nuclear receptor corepressor SMRT, silencing mediator of retinoic and thyroid hormone receptors.

The two families of receptors differ from each other considerably, and RARs show greater sequence homology with thyroid hormone receptors than with RXRs. RARs act only as heterodimers with RXRs homodimers of RARs have poor affinity for retinoid response elements on DNA. The liganded CRABP(II) enhances the binding of the RAR-RXR heterodimer to response elements on DNA and amplifies the effect of the receptor dimer (Delva et al., 1999). 

The vitamin D receptor- RXR heterodimer binds in 5 RXR-VDR3 polarity to a direct repeat hormone response element However, the vitamin D receptor also forms heterodimers with the retinoic acid receptor and the thyroid hormone receptor. All three vitamin D receptor dimers can interact with either direct repeat or inverted palindromic hormone response elements. In heterodimers, the vitamin D receptor may be at the 5 -position or 3 -position, resulting in six types of activated vitamin D receptor dimers that can bind to two types of response elements, raising the possibility of multiple signaling pathways (Carlberg, 1996 Carlberg et al., 2001 Yamada et al., 2001b). 

Leng, X., Blanco, J., Tsai, S., Ozato, K O Malley, B. W., and Tsai, M.-J. (1994). Mechanisms for synergistic activation of thyroid hormone receptor and retinoid X receptor on different response elements. J. Hrof. diem. 269, 31436-31442-... 

Thyroid response elements TRE A domain on deoxyribonucleic acid (DNA) that will bind the complex formed by thyroid hormone binding to the thyroid hormone receptor. When the complex binds to the TRE, which are located in the promoter region of the DNA, it activates transcription of the gene. When thyroid hormone is not bound to the receptor the receptor acts as a transcription repressor. 

Some nuclear-receptor response elements, such as those for the receptors that bind vitamin D3, thyroid hormone, and retinoic acid, are direct repeats of the same sequence recognized by the estrogen receptor, separated by three to five base pairs (Figure ll-42c-e). The specificity for responding to these different hormones by binding distinct receptors Is determined by the spacing between the repeats. The receptors that bind to such direct-repeat response elements do so as heterodimers with a common nuclear-receptor monomer called RXR. The vitamin D3 response element, for example, Is bound by the RXR-VDR heterodimer. 

A FIGURE 11-42 Consensus sequences of DNA response elements that bind three nuclear receptors. The response elements for the glucocorticoid receptor (GRE) and estrogen receptor (ERE) contain inverted repeats that bind these homodimeric proteins. The response elements for heterodimeric receptors contain a common direct repeat separated by three to five base pairs, for the vitamin D3 receptor (VDRE), thyroid hormone receptor (TRE), and retinoic acid receptor (RARE). The repeat sequences are indicated by red arrows. [See K. Umesono etal., 1991, Ce//65 1255, and A. M. Naaretal., 1991, Ce//65 1267]... 

Most of the intracellular receptors reside principally in the nucleus, and some of these are constitutively bound, as dimers, to their response element in DNA (e.g., the thyroid hormone receptor). Binding of the hormone changes its activity and its ability to associate with, or disassociate from, DNA. Regulation of gene transcription by these receptors is described in Chapter 16. 

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