Yorkie 通过招募一种组蛋白甲基转移酶复合物来促进转录。
Yorkie promotes transcription by recruiting a histone methyltransferase complex.
作者信息
Oh Hyangyee, Slattery Matthew, Ma Lijia, White Kevin P, Mann Richard S, Irvine Kenneth D
机构信息
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, HHSC 1104, New York, NY 10032, USA; Institute for Genomics and Systems Biology and Department of Human Genetics, University of Chicago, 900 East 57th Street, KCBD 10115, Chicago, IL 60637, USA.
出版信息
Cell Rep. 2014 Jul 24;8(2):449-59. doi: 10.1016/j.celrep.2014.06.017. Epub 2014 Jul 10.
Hippo signaling limits organ growth by inhibiting the transcriptional coactivator Yorkie. Despite the key role of Yorkie in both normal and oncogenic growth, the mechanism by which it activates transcription has not been defined. We report that Yorkie binding to chromatin correlates with histone H3K4 methylation and is sufficient to locally increase it. We show that Yorkie can recruit a histone methyltransferase complex through binding between WW domains of Yorkie and PPxY sequence motifs of NcoA6, a subunit of the Trithorax-related (Trr) methyltransferase complex. Cell culture and in vivo assays establish that this recruitment of NcoA6 contributes to Yorkie's ability to activate transcription. Mammalian NcoA6, a subunit of Trr-homologous methyltransferase complexes, can similarly interact with Yorkie's mammalian homolog YAP. Our results implicate direct recruitment of a histone methyltransferase complex as central to transcriptional activation by Yorkie, linking the control of cell proliferation by Hippo signaling to chromatin modification.
Hippo信号通路通过抑制转录辅激活因子Yorkie来限制器官生长。尽管Yorkie在正常生长和致癌生长中都起着关键作用，但其激活转录的机制尚未明确。我们报告称，Yorkie与染色质的结合与组蛋白H3K4甲基化相关，并且足以在局部增加这种甲基化。我们表明，Yorkie可以通过Yorkie的WW结构域与NcoA6（Trithorax相关（Trr）甲基转移酶复合体的一个亚基）的PPxY序列基序之间的结合来招募组蛋白甲基转移酶复合体。细胞培养和体内实验证实，NcoA6的这种招募有助于Yorkie激活转录的能力。哺乳动物的NcoA6是Trr同源甲基转移酶复合体的一个亚基，它同样可以与Yorkie的哺乳动物同源物YAP相互作用。我们的结果表明，直接招募组蛋白甲基转移酶复合体是Yorkie转录激活的核心，将Hippo信号通路对细胞增殖的控制与染色质修饰联系起来。
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