Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13
Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13
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DOI：
10.1073/pnas.0709749105
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发表时间：
2008-05-06
影响因子：
11.1
通讯作者：
Treisman, Jessica E.
中科院分区：
文献类型：
--
作者：
Carrera, Ines;Janody, Florence;Treisman, Jessica E.
Writ靶基因转录由稳定的β-连环蛋白的核转位介导，其结合TCF并招募Pygopus，一种作用机制未知的辅因子。介体复合物对于RNA聚合酶II依赖性基因的转录是必不可少的;它与由Med 12、Med 13、Cdk 8和细胞周期蛋白C亚基组成的辅助亚复合物相关联。我们在这里表明，果蝇介体复合物的Med 12和Med 13亚基，由kohtalo和skuld编码，是无翅靶基因转录所必需的。Kohtalo和Skuld在体内和细胞培养中均在β-连环蛋白稳定化的下游起作用。它们是由Pygopus的N-末端结构域转录激活所必需的，并且它们与Pygopus的物理相互作用取决于该结构域。我们建议，Pygopus促进Writ靶基因的转录通过招募中介复合物，通过与Med 12和Med 13的相互作用。
Writ target gene transcription is mediated by nuclear translocation of stabilized beta-catenin, which binds to TCF and recruits Pygopus, a cofactor with an unknown mechanism of action. The mediator complex is essential for the transcription of RNA polymerase II-dependent genes; it associates with an accessory subcomplex consisting of the Med12, Med13, Cdk8, and Cyclin C subunits. We show here that the Med12 and Med13 subunits of the Drosophila mediator complex, encoded by kohtalo and skuld, are essential for the transcription of Wingless target genes. kohtalo and skuld act downstream of beta-catenin stabilization both in vivo and in cell culture. They are required for transcriptional activation by the N-terminal domain of Pygopus, and their physical interaction with Pygopus depends on this domain. We propose that Pygopus promotes Writ target gene transcription by recruiting the mediator complex through interactions with Med12 and Med13.