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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer
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JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer

机译：JARID1B是在前列腺癌中上调的组蛋白H3赖氨酸4去甲基酶

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摘要

Histone methylation is a dynamic process that participates in a diverse array of cellular processes and has been found to associate with cancer. Recently, several histone demethylases have been identified that catalyze the removal of methylation from histone H3 lysine residues. Through bioinformatic and biochemical analysis, we identified JARID1B as a H3K4 demethylase. Overexpression of JARID1B resulted in loss of tri-, di-, and monomethyl H3K4 but did not affect other histone lysine methylations. In vitro biochemical experiments demonstrated that JARID1B directly catalyzes the demethylation. The enzymatic activity requires the JmjC domain and uses Fe(II) and a-ketoglutarate as cofactors. Furthermore, we found that JARID1B is up-regulated in prostate cancer tissues, compared with benign prostate samples. We also demonstrated that JARID1B associates with androgen receptor and regulates its transcriptional activity. Thus, we identified JARID1B as a demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer.
机译：组蛋白甲基化是一个动态过程，它参与各种细胞过程，并已发现与癌症有关。最近，已鉴定出几种组蛋白脱甲基酶，它们催化从组蛋白H3赖氨酸残基上去除甲基化。通过生物信息学和生化分析，我们确定JARID1B为H3K4脱甲基酶。 JARID1B的过表达导致三，三和单甲基H3K4丢失，但不影响其他组蛋白赖氨酸甲基化。体外生化实验表明，JARID1B直接催化脱甲基。酶促活性需要JmjC结构域，并使用Fe（II）和α-酮戊二酸酯作为辅助因子。此外，我们发现与良性前列腺样品相比，JARID1B在前列腺癌组织中上调。我们还证明了JARID1B与雄激素受体缔合并调节其转录活性。因此，我们将JARID1B确定为能够从组蛋白H3赖氨酸4中去除三个甲基并在前列腺癌中上调的脱甲基酶。

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