Enhanced histone H3K9 tri-methylation suppresses steroidogenesis in rat testis chronically exposed to arsenic
Enhanced histone H3K9 tri-methylation suppresses steroidogenesis in rat testis chronically exposed to arsenic
复制标题
增强的组蛋白 H3K9 三甲基化抑制长期暴露于砷的大鼠睾丸中的类固醇生成
DOI：
10.1016/j.ecoenv.2018.12.035
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发表时间：
2019-04-15
影响因子：
6.8
通讯作者：
Shen, Heqing
中科院分区：
文献类型：
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作者：
Alamdar, Ambreen;Tian, Meiping;Shen, Heqing
砷具有严重的健康风险，包括长期接触时会导致男性生殖功能障碍。组蛋白甲基化是一个重要的表观遗传学驱动因素；然而，它在砷诱导的类固醇合成发病机制中的作用仍不清楚。在本研究中，我们研究了组蛋白H3K9三甲基化(H3K9me3)对长期砷暴露后大鼠睾丸类固醇合成基因表达模式的影响。我们的结果显示，砷暴露下调了所有已研究的类固醇合成基因(LHR、Star、P450scc、Hsd3b、CyP17A1、Hsd17b和arom)的mRNA表达。此外，砷还能显著增加大鼠睾丸中H3K9me3的水平。H3K9me3升高的合理解释是组蛋白H3K9me3甲基转移酶SUV39H1上调和去甲基酶Jmjd2a下调。由于H3K9me3的激活导致基因抑制，我们进一步研究了类固醇合成基因的下调是否归因于H3K9me3水平的升高。为了阐明这一点，我们检测了类固醇合成基因启动子中H3K9me3的水平，这也表明在砷暴露后，调查地区H3K9me3的水平显著增加。综上所述，砷暴露通过激活H3K9me3状态抑制类固醇合成基因的表达，从而导致大鼠睾丸类固醇合成抑制。
Arsenic poses a profound health risk including male reproductive dysfunction upon prolonged exposure. Histone methylation is an important epigenetic driver; however, its role in arsenic- induced steroidogenic pathogenesis remains obscure. In current study, we investigated the effect of histone H3K9 tri-methylation (H3K9me3) on expression pattern of steroidogenic genes in rat testis after long-term arsenic exposure. Our results revealed that arsenic exposure down-regulated the mRNA expressions of all studied steroidogenic genes (Lhr, Star, P450scc, Hsd3b, Cyp17a1, Hsd17b and Arom). Moreover, arsenic significantly increased the H3K9me3 level in rat testis. The plausible explanation of increased H3K9me3 was attributable to the up-regulation of histone H3K9me3 methyltransferase, Suv39h1 and down-regulation of demethylase, Jmjd2a. Since H3K9me3 activation leads to gene repression, we further investigated whether the down-regulation of steroidogenic genes was ascribed to the increased H3K9me3 level. To elucidate this, we determined the H3K9me3 levels in steroidogenic gene promoters, which also showed significant increase of H3K9me3 in the investigated regions after arsenic exposure. In conclusion, arsenic exposure suppressed the steroidogenic gene expression by activating H3K9me3 status, which contributed to steroidogenic inhibition in rat testis.