Klose Robert J, Yan Qin, Tothova Zuzana, Yamane Kenichi, Erdjument-Bromage Hediye, Tempst Paul, Gilliland D Gary, Zhang Yi, Kaelin William G
Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell. 2007 Mar 9;128(5):889-900. doi: 10.1016/j.cell.2007.02.013. Epub 2007 Feb 22.
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.
组蛋白甲基化状态的改变可调节染色质结构以及诸如转录等依赖于DNA的过程。最近的研究表明，与其他组蛋白修饰类似，组蛋白甲基化是可逆的。视网膜母细胞瘤结合蛋白2（RBP2）是一种核蛋白，与视网膜母细胞瘤肿瘤抑制蛋白对转录和分化的调控有关，它包含一个最近被定义为组蛋白去甲基化酶特征基序的JmjC结构域。在此我们报告，RBP2是一种去甲基化酶，它特异性地催化H3K4的去甲基化，而H3K4的甲基化通常与转录活性基因相关。RBP2基因敲除小鼠细胞显示某些细胞因子基因的转录增强，就基质细胞衍生因子1（SDF1）而言，这与H3K4三甲基化增加有关。此外，在生化和基于细胞的实验中，RBP2特异性地使H3K4去甲基化。这些研究为RBP2的转录调控提供了机制上的见解，并提供了首个能够去除三甲基化H3K4的哺乳动物酶的实例。
