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| H-2RIIBP (RXR-BETA) HETERODIMERIZATION PROVIDES A MECHANISM FOR COMBINATORIAL DIVERSITY IN THE REGULATION OF RETINOIC ACID AND THYROID-HORMONE RESPONSIVE GENES |
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| Author(s): MARKS MS, HALLENBECK PL, NAGATA T, SEGARS JH, APPELLA E, NIKODEM VM, OZATO K |
| Source: EMBO JOURNAL Volume: 11 Issue: 4 Pages: 1419-1435 Published: APR 1992 |
| Times Cited: 451 References: 81 |
| Abstract: H-2RIIBP (RXR-beta) is a member of the nuclear hormone receptor superfamily that activates transcription of NHC class I genes in response to retinoic acid (RA). Using chemical cross-linking, co-immunoprecipitation, gel mobility shift and streptavidin - biotin DNA precipitation assays, we show that H-2RIIBP formed heterodimers with thyroid hormone (T3) and RA receptors (T3R-alpha and RAR-alpha). H-2RIIBP heterodimer formation required a conserved sub-domain of its C-terminal region, occurred independently of target DNA and was much more efficient than either T3R-alpha/RAR-alpha heterodimer or H-2RIIBP homodimer formation. Heterodimers displayed enhanced binding to target DNA elements and contacted DNA in a manner distinct from that of homodimers. A functional role for heterodimers in vivo was demonstrated by synergistic enhancement of MHC class I transcription following co-transfection of H-2RIIBP with T3R-alpha or RAR-alpha. We provide biochemical evidence that H-2RIIBP formed heterodimers with several naturally occurring nuclear proteins. The results suggest that H-2RIIBP, by virtue of its ability to heterodimerize, enhances combinatorial diversity and versatility in gene regulation mediated by nuclear hormone receptors. |
| Document Type: Article |
| Language: English |
Addresses:
1. NICHHD, MOLEC GROWTH REGULAT LAB, BETHESDA, MD 20892 USA 2. NIDDKD, GENET & BIOCHEM BRANCH, BETHESDA, MD 20892 USA 3. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: HM836 |
| ISSN: 0261-4189 |
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