The retinoblastoma binding protein RBP2 is an H3K4 demethylase
The retinoblastoma binding protein RBP2 is an H3K4 demethylase
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DOI：
10.1016/j.cell.2007.02.013
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发表时间：
2007-03-09
期刊：
影响因子：
64.5
通讯作者：
Kaelin, William G., Jr.
中科院分区：
文献类型：
--
作者：
Klose, Robert J.;Yan, Qin;Kaelin, William G., Jr.
组蛋白甲基化状态的变化调节染色质结构和DNA依赖性过程，例如转录。最近的研究表明，类似于其他组蛋白修饰，组蛋白甲基化是可逆的。视网膜母细胞瘤结合蛋白2（RBP2）是一种与视网膜细胞瘤肿瘤抑制蛋白调节转录和分化有关的核蛋白，其中包含最近定义为组蛋白脱甲基酶特征基序的JMJC结构域。在这里，我们报告RBP2是一种特异性催化H3K4脱甲基化的脱甲基酶，其甲基化通常与转录活性基因相关。 RBP2 - / - 小鼠细胞表现出增强的某些细胞因子基因的转录，在SDF1的情况下，它们与H3K4三甲基化增加有关。此外，RBP2在生化和基于细胞的测定中特异性去甲基化的H3K4。这些研究提供了RBP2对转录调控的机械见解，并提供了能够消除三甲基化H3K4的哺乳动物酶的第一个例子。
Changes in histone methylation status regulate chromatin structure and DNA-dependent processes such as transcription. Recent studies indicate that, analogous to other histone modifications, histone methylation is reversible. Retinoblastoma binding protein 2 (RBP2), a nuclear protein implicated in the regulation of transcription and differentiation by the retinoblastoma tumor suppressor protein, contains a JmjC domain recently defined as a histone demethylase signature motif. Here we report that RBP2 is a demethylase that specifically catalyzes demethylation on H3K4, whose methylation is normally associated with transcriptionally active genes. RBP2-/- mouse cells displayed enhanced transcription of certain cytokine genes, which, in the case of SDF1, was associated with increased H3K4 trimethylation. Furthermore, RBP2 specifically demethylated H3K4 in biochemical and cell-based assays. These studies provide mechanistic insights into transcriptional regulation by RBP2 and provide the first example of a mammalian enzyme capable of erasing trimethylated H3K4.