H-2RIIBP (RXR-BETA) HETERODIMERIZATION PROVIDES A MECHANISM FOR COMBINATORIAL DIVERSITY IN THE REGULATION OF RETINOIC ACID AND THYROID-HORMONE RESPONSIVE GENES
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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DOI：
10.1002/j.1460-2075.1992.tb05187.x
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发表时间：
1992-04-01
期刊：
影响因子：
11.4
通讯作者：
OZATO, K
中科院分区：
文献类型：
--
作者：
MARKS, MS;HALLENBECK, PL;OZATO, K
H-2RIIBP (RXR-beta) 是核激素受体超家族的成员，可响应视黄酸 (RA) 激活 NHC I 类基因的转录。使用化学交联、免疫共沉淀、凝胶迁移率变化和链霉亲和素-生物素 DNA 沉淀测定，我们表明 H-2RIIBP 与甲状腺激素 (T3) 和 RA 受体（T3R-α 和 RAR-α）形成异二聚体。 H-2RIIBP 异二聚体的形成需要其 C 端区域的保守子结构域，独立于靶 DNA 发生，并且比 T3R-α/RAR-α 异二聚体或 H-2RIIBP 同二聚体形成更有效。异二聚体与靶 DNA 元件的结合增强，并以与同二聚体不同的方式接触 DNA。 H-2RIIBP 与 T3R-α 或 RAR-α 共转染后，MHC I 类转录的协同增强证明了异二聚体在体内的功能作用。我们提供的生化证据表明 H-2RIIBP 与几种天然存在的核蛋白形成异二聚体。结果表明，H-2RIIBP 凭借其异二聚化能力，增强了核激素受体介导的基因调控的组合多样性和多功能性。
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.