Horard B, Castet A, Bardet P-L, Laudet V, Cavailles V, Vanacker J-M
Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR 5161, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69007 Lyon, France.
J Mol Endocrinol. 2004 Oct;33(2):493-509. doi: 10.1677/jme.1.01538.
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.
雌激素受体相关（ERR）受体是核受体超家族的孤儿成员，它们作为同二聚体与特定的DNA靶位点结合。然而，尚未证明这种结合模式是否是它们驱动的转录激活所必需的。我们在此表明，这些受体之间也可发生异二聚化。此外，我们证明ERR基因独特的文昌鱼直系同源物（AmphiERR）以两种因框内插入而不同的异构体形式表达。虽然短异构体的行为与其哺乳动物对应物相似，但长异构体（AmphiERR(L)）根据其结合的靶位点显示出不同的转录特性。实际上，AmphiERR(L)以单体形式结合，但不通过SF1反应元件（SFRE）激活转录。相反，这种异构体以同二聚体形式结合并通过经典的雌激素反应元件激活转录。我们的结果强烈表明，二聚化是ERR受体发挥反式激活作用所必需的。
