RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3
RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3
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DOI：
10.1016/j.cell.2007.02.003
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发表时间：
2007-03-23
期刊：
影响因子：
64.5
通讯作者：
Helin, Kristian
中科院分区：
文献类型：
--
作者：
Christensen, Jesper;Agger, Karl;Helin, Kristian
组蛋白甲基化；被认为是一种稳定的修饰，定义了细胞的表观遗传程序，调节染色质结构和转录。然而，最近发现的组蛋白去甲基化酶对组蛋白甲基化的稳定性提出了挑战。在这里，我们证明了JARID1蛋白RBP2， PLU1和SMCX是组蛋白去甲基化酶特异性的二甲基化和三甲基化组蛋白3赖氨酸4 （H3K4）。与JARID1果蝇同源Lid在发育过程中调节同源基因表达的作用一致，我们发现RBP2在胚胎干（ES）细胞分化过程中从Hox基因中移位，与它们的H3K4me3水平和表达的增加相关。此外，我们发现秀丽隐杆线虫JARID1同源物br-2的突变或RNAi缺失导致幼虫发育过程中H3K4me3水平升高和外阴形成缺陷。综上所述，这些结果表明JARID1家族调控的H3K4me3/me2去甲基化在发育过程中起重要作用。
Methylation of histones; has been regarded as a stable modification defining the epigenetic program of the cell, which regulates chromatin structure and transcription. However, the recent discovery of histone demethylases has challenged the stable nature of histone methylation. Here we demonstrate that the JARID1 proteins RBP2, PLU1, and SMCX are histone demethylases specific for di- and trimethylated histone 3 lysine 4 (H3K4). Consistent with a role for the JARID1 Drosophila homolog Lid in regulating expression of homeotic genes during development, we show that RBP2 is displaced from Hox genes during embryonic stem (ES) cell differentiation correlating with an increase of their H3K4me3 levels and expression. Furthermore, we show that mutation or RNAi depletion of the C. elegans JARID1 homolog rbr-2 leads to increased levels of H3K4me3 during larval development and defects in vulva formation. Taken together, these results suggest that H3K4me3/me2 demethylation regulated by the JARID1 family plays an important role during development.