A Jumonji (Jarid2) Protein Complex Represses cyclin D1 Expression by Methylation of Histone H3-K9
A Jumonji (Jarid2) Protein Complex Represses cyclin D1 Expression by Methylation of Histone H3-K9
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DOI：
10.1074/jbc.m804994200
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发表时间：
2009-01-09
影响因子：
4.8
通讯作者：
Takeuchi, Takashi
中科院分区：
文献类型：
--
作者：
Shirato, Haruki;Ogawa, Satoko;Takeuchi, Takashi
组蛋白尾部的共价修饰在调节基因表达中具有关键作用。以前，我们确定了jumonji（jmj，Jarid 2）基因，jmjC结构域，和Jmj家族。最近，许多Jmj家族蛋白已被证明是组蛋白去甲基化酶，而jmjC是催化结构域。然而，Jmj不具有组蛋白脱甲基酶活性，因为jmjC结构域缺乏用于结合辅因子的保守残基。独立于这些研究，我们以前表明，JMJ结合到细胞周期蛋白D1启动子和抑制细胞周期蛋白D1的转录。在这里，我们展示了Jmj抑制细胞周期蛋白D1转录的机制。我们发现Jmj的蛋白复合物具有针对组蛋白H3赖氨酸9（H3-K9）的组蛋白甲基转移酶活性。我们还发现Jmj与H3-K9甲基转移酶G9 a和GLP结合。Jmj的表达将G9 a和GLP募集到细胞周期蛋白D1启动子并增加H3-K9甲基化。G9 a和GLP的失活，但不仅G9 a，抑制细胞周期蛋白D1启动子中H3-K9的甲基化和细胞周期蛋白D1表达的抑制JMJ。这些结果表明，Jmj甲基化H3-K9和抑制细胞周期蛋白D1的表达，通过G9 a和GLP，Jmj家族蛋白可以调节基因的表达不仅通过组蛋白去甲基化，但也有其他组蛋白修饰。
Covalent modifications of histone tails have critical roles in regulating gene expression. Previously, we identified the jumonji (jmj, Jarid2) gene, the jmjC domain, and a Jmj family. Recently, many Jmj family proteins have been shown to be histone demethylases, and jmjC is the catalytic domain. However, Jmj does not have histone demethylase activity because the jmjC domain lacks conserved residues for binding to cofactors. Independently of these studies, we previously showed that Jmj binds to the cyclin D1 promoter and represses the transcription of cyclin D1. Here, we show the mechanisms by which Jmj represses the transcription of cyclin D1. We found that a protein complex of Jmj had histone methyltransferase activity toward histone H3 lysine 9 (H3-K9). We also found that Jmj bound to the H3-K9 methyltransferases G9a and GLP. Expression of Jmj recruited G9a and GLP to the cyclin D1 promoter and increased H3-K9 methylation. Inactivation of both G9a and GLP, but not of only G9a, inhibited the methylation of H3-K9 in the cyclin D1 promoter and repression of cyclin D1 expression by Jmj. These results suggest that Jmj methylates H3-K9 and represses cyclin D1 expression through G9a and GLP, and that Jmj family proteins can regulate gene expression by not only histone demethylation but also other histone modification.