Arsenite downregulates H3K4 trimethylation and H3K9 dimethylation during transformation of human bronchial epithelial cells
Arsenite downregulates H3K4 trimethylation and H3K9 dimethylation during transformation of human bronchial epithelial cells
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DOI：
10.1002/jat.3555
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发表时间：
2018-04
影响因子：
3.3
通讯作者：
W. Tu;Yin Liu;Chengfeng Xie;Xue Zhou
中科院分区：
文献类型：
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作者：
W. Tu;Yin Liu;Chengfeng Xie;Xue Zhou
砷是一种公认的人类致癌物，但具有弱的致突变活性。砷诱导的致癌机制尚未完全了解。在本研究中，我们研究了组蛋白甲基化在人支气管上皮（BEAS-2B）细胞转化中的作用。16周后，用0.1、0.5和1 μm的亚砷酸盐处理细胞。0.1 μm的亚砷酸盐在12周时降低了H3 K4（H3 K4 me 3）的总三甲基化水平，而0.5和1 μm的亚砷酸盐在8、12和16周时降低了H3 K4的总三甲基化水平，这可能是由于组蛋白甲基转移酶活性降低、组蛋白去甲基化酶（HDM）活性升高以及H3 K4去甲基化酶KDM 5A蛋白水平升高所致。0.5 μm砷暴露4、8、12和16周以及1.0 μm砷暴露8和12周后，H3 K9的二甲基化水平（H3 K9 me 2）也有所下降，这与HDM活性的增加有关。我们的研究结果表明，亚砷酸盐通过调节组蛋白甲基转移酶和/或HDMs的酶活性，以及通过上调H3 K4 me 3的KDM 5A蛋白水平，在细胞转化过程中降低了H3 K4 me 3和H3 K9 me 2的水平。
Arsenic is an established human carcinogen but with weak mutagenic activity. The mechanisms of arsenic‐induced carcinogenesis are not well understood. In the present study, we investigated the role of histone methylation in transformation of human bronchial epithelial (BEAS‐2B) cells. After 16 weeks’ exposure, cells were transformed by 0.1, 0.5 and 1 μm arsenite. Global trimethylated H3K4 (H3K4me3) was decreased by 0.1 μm arsenite at 12 weeks, and 0.5 and 1 μm arsenite at 8, 12 and 16 weeks, which could be attributed to reduced histone methyltransferase activities, increased histone demethylase (HDM) activities as well as increased protein levels of H3K4 demethylase KDM5A. Global dimethylated H3K9 (H3K9me2) was also decreased after exposure to 0.5 μm arsenite for 4, 8, 12 and 16 weeks and 1.0 μm arsenite for 8 and 12 weeks, which was associated with an increase of HDM activities. Our findings indicated that arsenite decreased global H3K4me3 and H3K9me2 levels during cell transformation by modulating the enzymatic activities of histone methyltransferases and/or HDMs, and by upregulation of KDM5A protein levels for H3K4me3.