Dimerization is required for transactivation by estrogen-receptor-related (ERR) orphan receptors: evidence from amphioxus ERR
Dimerization is required for transactivation by estrogen-receptor-related (ERR) orphan receptors: evidence from amphioxus ERR
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DOI：
10.1677/jme.1.01538
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发表时间：
2004-10-01
影响因子：
3.5
通讯作者：
Vanacker, JM
中科院分区：
文献类型：
--
作者：
Horard, B;Castet, A;Vanacker, JM
雌激素受体相关(ERR)受体是核受体超家族中的孤儿成员，以同源二聚体的形式与其特定的DNA靶点结合。然而，目前还没有表明这种结合模式是否需要它们驱动的转录激活。我们在这里表明，异二聚化也可以发生在这些受体之间。此外，我们还证明了ERR基因的独特的文昌鱼同源基因(AmphiERR)被表达为两种不同的异构体，通过框架内插入而不同。短异构体的行为与哺乳动物的异构体相似，而长异构体(L)根据其结合的靶位显示出不同的转录特性。事实上，AmphiERR(L)以单体的形式结合，但不通过SF1反应元件激活转录。相反，这种异构体以同源二聚体的形式结合，并通过经典的雌激素反应元件激活转录。我们的结果有力地表明，ERR受体的反式激活需要二聚化。
The estrogen-receptor-related (ERR) receptors are orphan members of the nuclear receptor superfamily that bind to their specific DNA target sites as homodimers. However, it has not been shown whether this mode of binding is required for the transcriptional activation they drive. We here show that heterodimerization can also occur between these receptors. Furthermore, we demonstrate that the unique amphioxus ortholog of ERR genes (AmphiERR) is expressed as two isoforms differing by an in-frame insertion. While the short isoform behaves like its mammalian counterparts, the long isoform (AmphiERR(L)) displays divergent transcriptional properties according to the target site to which it binds. Indeed, AmphiERR(L) binds as a monomer but does not activate transcription through the SF1 response element (SFRE). On the contrary, this isoform binds as a homodimer and activates transcription through the classical estrogen-response element. Our results strongly suggest that dimerization is required for transactivation exerted by the ERR receptors.