Negative regulation of hypoxic responses via induced Reptin methylation.
Negative regulation of hypoxic responses via induced Reptin methylation.
复制标题
DOI：
10.1016/j.molcel.2010.06.008
复制
发表时间：
2010-07-09
期刊：
影响因子：
16
通讯作者：
Baek SH
中科院分区：
文献类型：
--
作者：
Lee JS;Kim Y;Kim IS;Kim B;Choi HJ;Lee JM;Shin HJ;Kim JH;Kim JY;Seo SB;Lee H;Binda O;Gozani O;Semenza GL;Kim M;Kim KI;Hwang D;Baek SH
组蛋白中的赖氨酸甲基化对于转录调控至关重要，因此将染色质状态与生物学结果联系起来。虽然最近的研究已经将赖氨酸甲基化扩展到非组蛋白蛋白，但潜在的分子机制，如诱导赖氨酸甲基化的上游信号级联和受此修饰调节的下游靶基因尚未阐明。在这里，我们表明，Reptin，染色质重塑因子，是甲基化在赖氨酸67在缺氧条件下的甲基转移酶G9a。甲基化的Reptin与低氧应答基因的一个子集的启动子结合并负调节这些基因的转录以调节细胞对低氧的应答。
Lysine methylation within histones is crucial for transcriptional regulation and thus links chromatin states to biological outcomes. Although recent studies have extended lysine methylation to nonhistone proteins, underlying molecular mechanisms such as the upstream signaling cascade that induces lysine methylation and downstream target genes modulated by this modification have not been elucidated. Here, we show that Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. Methylated Reptin binds to the promoters of a subset of hypoxia-responsive genes and negatively regulates transcription of these genes to modulate cellular responses to hypoxia.