Journal article
DNA-independent and DNA-dependent Mechanisms Regulate the Differential Heterodimerization of the Isoforms of the Thyroid Hormone Receptor with Retinoid X Receptor
The Journal of biological chemistry, v 271(45), pp 28199-28205
08 Nov 1996
PMID: 8910436
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Thyroid hormone receptors (TRs) require heterodimerization with retinoid X receptor (RXR) for maximum DNA binding affinity. Interaction with RXR occurs via two dimerization interfaces, one in the DNA-binding domain and one in the C-terminal “ninth heptad” of the receptors. We studied the relative importance of these two dimerization domains in naturally occurring C-terminal TR variants. TRα1 has a conserved ninth heptad and formed stable heterodimers with RXR in solution. TRα1·RXR heterodimers bound similarly to direct repeat 4 (DR4) sites with different 5′-flanking and spacer sequences. In contrast, TRα2, which contains a highly divergent ninth heptad, did not interact with RXR in solution and bound as a heterodimer with RXR only to specific DR4 sequences in which the downstream half-site was the preferred octameric binding site of TR (TNAGGTCA). Although the ninth heptad of TRα2 was insufficient for interaction with RXR off DNA, this region was required for DNA-dependent heterodimerization with RXR. TRα3, another naturally occurring TRα isoform whose ninth heptad differs from those of both TRα1 and TRα2, displayed intermediate behavior in heterodimerization with RXR. Thus, in the absence of a strong ninth heptad interaction an octameric downstream half-site allosterically promotes RXR heterodimerization with TRα2. Differential dependence upon DNA-binding for heterodimerization with RXR may influence transcriptional regulation by TRα isoforms.
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Details
- Title
- DNA-independent and DNA-dependent Mechanisms Regulate the Differential Heterodimerization of the Isoforms of the Thyroid Hormone Receptor with Retinoid X Receptor
- Creators
- Mauricio J. Reginato - University of PennsylvaniaJinsong ZhangMitchell A. Lazar - University of Pennsylvania
- Publication Details
- The Journal of biological chemistry, v 271(45), pp 28199-28205
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:A1996VU03300036
- Scopus ID
- 2-s2.0-0029946449
- Other Identifier
- 991020100080304721
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- Web of Science research areas
- Biochemistry & Molecular Biology