RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation
RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation
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DOI：
10.1111/j.1365-2443.2007.01089.x
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发表时间：
2007-06-01
期刊：
影响因子：
2.1
通讯作者：
Nakayama, Jun-ichi
中科院分区：
文献类型：
--
作者：
Hayakawa, Tomohiro;Ohtani, Yasuko;Nakayama, Jun-ichi
MRG 15是一种保守的染色体结构域蛋白，与组蛋白脱乙酰酶（HDAC）和含Tip 60的组蛋白乙酰转移酶（HAT）复合物相关。在这里，我们进一步表征MRG 15的复合物，并显示MRG 15和组蛋白H3 K4去甲基化酶活性在哺乳动物细胞中的功能联系。MRG 15主要定位于富含Ser（2）-磷酸化RNA聚合酶II的离散核亚结构域，表明其特异性参与活性转录。对含MRG 15的复合物进行蛋白质分析，鉴定出RBP 2，一种含JmjC结构域的蛋白质。值得注意的是，RBP 2的过表达大大降低了体内培养的人类细胞中的H3 K4甲基化，并且重组RBP 2在体外有效地去除了组蛋白尾部的H3 K4甲基化。RBP 2的敲低导致活性基因转录区域内H3 K4甲基化水平增加。我们的研究结果表明，RBP 2与MRG 15复合物相关，以维持转录区域H3 K4甲基化的降低，这可能确保转录延伸状态。
MRG15 is a conserved chromodomain protein that associates with histone deacetylases (HDACs) and Tip60-containing histone acetyltransferase (HAT) complexes. Here we further characterize MRG15-containing complexes and show a functional link between MRG15 and histone H3K4 demethylase activity in mammalian cells. MRG15 was predominantly localized to discrete nuclear subdomains enriched for Ser(2)-phosphorylated RNA polymerase II, suggesting it is involved specifically with active transcription. Protein analysis of the MRG15-containing complexes led to the identification of RBP2, a JmjC domain-containing protein. Remarkably, over-expression of RBP2 greatly reduced the H3K4 methylation in culture human cells in vivo, and recombinant RBP2 efficiently removed H3K4 methylation of histone tails in vitro. Knockdown of RBP2 resulted in increased H3K4 methylation levels within transcribed regions of active genes. Our findings demonstrate that RBP2 associated with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state.