Hamada K, Gleason S L, Levi B Z, Hirschfeld S, Appella E, Ozato K
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1989 Nov;86(21):8289-93. doi: 10.1073/pnas.86.21.8289.
Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, but not to other MHC cis-acting sequences or to mutant region II sequences, similar to the naturally occurring region II factor in mouse cells. The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors. Although sequence similarity in other regions was minimal, H-2RIIBP has apparent modular domains characteristic of the nuclear hormone receptors. Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene. The ERE is composed of a palindrome, and half of this palindrome resembles the region II binding site of the MHC CRE. These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences. Sequences homologous to the H-2RIIBP gene are widely conserved in the animal kingdom. H-2RIIBP mRNA is expressed in many mouse tissues, in agreement with the distribution of the natural region II factor.
主要组织相容性复合体（MHC）I类基因的转录受保守的MHC I类调节元件（CRE）调控。CRE有两个因子结合位点，即区域I和区域II，二者均具有增强子功能。通过用CRE作为探针筛选小鼠λgt 11文库，我们分离出一个cDNA克隆，其编码的蛋白能够与CRE的区域II结合。这种蛋白，即H-2RIIBP（H-2区域II结合蛋白），与天然的区域II序列结合，但不与其他MHC顺式作用序列或突变的区域II序列结合，这与小鼠细胞中天然存在的区域II因子相似。H-2RIIBP推导的氨基酸序列显示出两个与类固醇/甲状腺激素受体的DNA结合结构域同源的假定锌指。尽管其他区域的序列相似性很小，但H-2RIIBP具有核激素受体特有的明显模块化结构域。进一步分析表明，H-2RIIBP和天然的区域II因子均与卵黄蛋白原A2基因的雌激素反应元件（ERE）结合。ERE由一个回文结构组成，该回文结构的一半类似于MHC CRE的区域II结合位点。这些结果表明，H-2RIIBP（i）是核激素受体超家族的成员，（ii）可能不仅调节MHC I类基因，还调节含有ERE及相关序列的基因。与H-2RIIBP基因同源的序列在动物界广泛保守。H-2RIIBP mRNA在许多小鼠组织中表达，这与天然区域II因子的分布一致。
