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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells
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Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells

机译:通过SET7介导的赖氨酸甲基化在哺乳动物细胞中调节DNMT1的稳定性

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摘要

Inheritance of epigenetic information encoded by cytosine DNA methylation patterns is crucial for mammalian cell survival, in large part through the activity of the maintenance DNA methyltrans-ferase (DNMT1). Here, we show that SET7, a known histone methyltransferase, is involved in the regulation of protein stability of DNMT1. SET7 colocalizes and directly interacts with DNMT1 and specifically monomethylates Lys-142 of DNMT1. Methylated DNMT1 peaks during the S and G_2 phases of the cell cycle and is prone to proteasome-mediated degradation. Overexpression of SET7 leads to decreased DNMT1 levels, and siRNA-mediated knockdown of SET7 stabilizes DNMT1. These results demonstrate that signaling through SET7 represents a means of DNMT1 enzyme turnover.
机译:由胞嘧啶DNA甲基化模式编码的表观遗传信息的传承对于哺乳动物细胞的生存至关重要,这在很大程度上取决于维持性DNA甲基转移酶(DNMT1)的活性。在这里,我们显示SET7,一种已知的组蛋白甲基转移酶,参与了DNMT1蛋白质稳定性的调节。 SET7共定位并直接与DNMT1相互作用,特别是与DNMT1的Lys-142单甲基化。甲基化的DNMT1在细胞周期的S和G_2阶段达到峰值,并易于蛋白酶体介导的降解。 SET7的过表达导致DNMT1水平降低,而siRNA介导的SET7敲低可稳定DNMT1。这些结果证明通过SET7的信号传导代表DNMT1酶更新的手段。

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