Androgen receptor regulation by histone methyltransferase Suppressor of variegation 3-9 homolog 2 and Melanoma antigen-A11.
Androgen receptor regulation by histone methyltransferase Suppressor of variegation 3-9 homolog 2 and Melanoma antigen-A11.
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DOI：
10.1016/j.mce.2016.12.028
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发表时间：
2017-03-05
影响因子：
4.1
通讯作者：
Wilson EM
中科院分区：
文献类型：
--
作者：
Askew EB;Bai S;Parris AB;Minges JT;Wilson EM
雄激素受体（AR）的转录活性取决于AR NH 2-末端区域和转录辅助调节因子之间的相互作用。以预测的α-螺旋NH 2-末端片段AR-（370-420）为诱饵，酵母双杂交筛选人睾丸文库，鉴定出杂色抑制子3-9同源物2（suppressor of variegation 3-9 homolog 2，SUV 39 H2）组蛋白甲基转移酶为AR相互作用蛋白。在双杂交、体外谷胱甘肽S-转移酶亲和基质和免疫共沉淀试验中验证了SUV 39 H2与AR和AR辅助调节因子黑色素瘤抗原-A11（MAGE-A11）的相互作用。荧光免疫细胞化学共定位SUV 39 H2和AR在不含雄激素的细胞质中、在含雄激素的细胞核中以及与MAGE-A11在不依赖雄激素的细胞核中。使用针对SUV 39 H2的抗体进行的染色质免疫沉淀证明了AR和SUV 39 H2对前列腺特异性抗原基因的雄激素响应性上游增强子的雄激素依赖性募集。SUV 39 H2与MAGE-A11协同作用以增加雄激素依赖性AR转录活性。SUV 39 H2组蛋白甲基转移酶是一种AR共激活因子，通过与AR和MAGE-A11相互作用增加雄激素依赖性转录活性。
Androgen receptor (AR) transcriptional activity depends on interactions between the AR NH2-terminal region and transcriptional coregulators. A yeast two-hybrid screen of a human testis library using predicted α-helical NH2-terminal fragment AR-(370–420) as bait identified suppressor of variegation 3–9 homolog 2 (SUV39H2) histone methyltransferase as an AR interacting protein. SUV39H2 interaction with AR and the AR coregulator, melanoma antigen-A11 (MAGE-A11), was verified in two-hybrid, in vitro glutathione S-transferase affinity matrix and coimmunoprecipitation assays. Fluorescent immunocytochemistry colocalized SUV39H2 and AR in the cytoplasm without androgen, in the nucleus with androgen, and with MAGE-A11 in the nucleus independent of androgen. Chromatin immunoprecipitation using antibodies raised against SUV39H2 demonstrated androgen-dependent recruitment of AR and SUV39H2 to the androgen-responsive upstream enhancer of the prostate-specific antigen gene. SUV39H2 functioned cooperatively with MAGE-A11 to increase androgen-dependent AR transcriptional activity. SUV39H2 histone methyltransferase is an AR coactivator that increases androgen-dependent transcriptional activity through interactions with AR and MAGE-A11.