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首页> 外文期刊>Molecular and Cellular Biology >The orphan receptor Rev-ErbA alpha activates transcription via a novel response element.
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The orphan receptor Rev-ErbA alpha activates transcription via a novel response element.

机译：孤儿受体Rev-ErbAα通过新型应答元件激活转录。

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Rev-ErbA alpha (Rev-Erb) is a nuclear hormone receptor-related protein encoded on the opposite strand of the alpha-thyroid hormone receptor (TR) gene. This unusual genomic arrangement may have a regulatory role, but the conservation of human and rodent Rev-Erb amino acid sequences suggests that the protein itself has an important function, potentially as a sequence-specific transcriptional regulator. However, despite its relationship to the TR, Rev-Erb bound poorly to TR binding sites. To determine its DNA-binding specificity in an unbiased manner, Rev-Erb was synthesized in Escherichia coli, purified, and used to select specific binding-sites from libraries of random double-stranded DNA sequences. We found that Rev-Erb binds to a unique site consisting of a specific 5-bp A/T-rich sequence adjacent to a TR half-site. Rev-Erb contacts this entire asymmetric 11-bp sequence, which is the longest nonrepetitive element specifically recognized by a member of the thyroid/steroid hormone receptor superfamily, and mutations in either the A/T-rich or TR half-site regions abolished specific binding. The binding specificity of wild-type Rev-Erb was nearly identical to that of C- and N-terminally truncated forms. This binding was not enhanced by retinoid X receptor, TR, or other nuclear proteins, none of which formed heterodimers with Rev-Erb. Rev-Erb also appeared to bind to the selected site as a monomer. Furthermore, Rev-Erb activates transcription through this binding site even in the absence of exogenous ligand. Thus, Rev-Erb is a transcriptional activator whose properties differ dramatically from those of classical nuclear hormone receptors, including the TR encoded on the opposite strand of the same genomic locus.
机译：Rev-ErbA alpha（Rev-Erb）是在α-甲状腺激素受体（TR）基因相反链上编码的核激素受体相关蛋白。这种异常的基因组排列可能具有调节作用，但是人类和啮齿动物的Rev-Erb氨基酸序列的保守性表明该蛋白本身具有重要的功能，可能作为序列特异性的转录调节剂。然而，尽管其与TR相关，但是Rev-Erb与TR结合位点的结合差。为了以无偏倚的方式确定其DNA结合特异性，Rev-Erb在大肠杆菌中合成，纯化并用于从随机双链DNA序列文库中选择特异性结合位点。我们发现Rev-Erb结合一个独特的位点，该位点由一个特定的5 bp富含A / T的序列组成，与TR半位点相邻。 Rev-Erb接触整个不对称的11 bp序列，这是甲状腺/类固醇激素受体超家族成员特异性识别的最长的非重复性元素，并且富含A / T或TR的半位点区域的突变被特异性消除捆绑。野生型Rev-Erb的结合特异性几乎与C和N末端截短形式的结合特异性相同。类视黄醇X受体，TR或其他核蛋白均未增强这种结合，它们均未与Rev-Erb形成异二聚体。 Rev-Erb也似乎以单体形式结合到所选位点。此外，即使在没有外源配体的情况下，Rev-Erb也会通过该结合位点激活转录。因此，Rev-Erb是一种转录激活剂，其性质与经典的核激素受体的性质显着不同，包括在相同基因组基因座相反链上编码的TR。

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