Transcriptional regulation of the human ferritin gene by coordinated regulation of Nrf2 and protein arginine methyltransferases PRMT1 and PRMT4
Transcriptional regulation of the human ferritin gene by coordinated regulation of Nrf2 and protein arginine methyltransferases PRMT1 and PRMT4
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DOI：
10.1096/fj.12-226043
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发表时间：
2013-09-01
期刊：
影响因子：
4.8
通讯作者：
Tsuji, Yoshiaki
中科院分区：
文献类型：
--
作者：
Huang, Bo-Wen;Ray, Paul D.;Tsuji, Yoshiaki
抗氧化基因如铁蛋白在氧化应激中通过抗氧化反应元件（are）转录激活，核因子e2相关因子2 （Nrf2）与are结合并激活转录。组蛋白修饰在转录调控中起着协同和重要的作用；然而，其在抗氧化基因转录中的作用尚不清楚。砷暴露通过ARE激活铁蛋白转录，同时增加组蛋白H4Arg3 （H4R3）和H3Arg17 （H3R17）的甲基化。为了验证我们关于组蛋白H4R3和H3R17甲基化调节铁蛋白转录的假设，我们研究了H4R3和H3R17蛋白精氨酸(R)甲基转移酶1和4 （PRMT1和PRMT4）。砷暴露于人HaCaT角质形成细胞诱导靠近ARE的PRMT1和PRMT4、组蛋白H4R3和H3R17甲基化的核积累，而不是铁蛋白基因的非ARE区域。PRMT1或PRMT4敲低并不会阻断Nrf2的核积累，但会抑制Nrf2与AREs的结合，降幅约为40% (P
Antioxidant genes such as ferritin are transcriptionally activated in oxidative stress via the antioxidant responsive element (ARE), to which nuclear factor-E2-related factor 2 (Nrf2) binds and activates transcription. Histone modification plays a cooperative and essential role in transcriptional regulation; however, its role in antioxidant gene transcription remains elusive. Arsenic exposure activated ferritin transcription via the ARE concomitant with increased methylation of histones H4Arg3 (H4R3) and H3Arg17 (H3R17). To test our hypothesis that histone H4R3 and H3R17 methylation regulates ferritin transcription, H4R3 and H3R17 protein arginine (R) methyltransferases 1 and 4 (PRMT1 and PRMT4) were investigated. Arsenic exposure of human HaCaT keratinocytes induced nuclear accumulation of PRMT1 and PRMT4, histone H4R3 and H3R17 methylation proximal to the ARE, but not to the non-ARE regions of ferritin genes. PRMT1 or PRMT4 knockdown did not block Nrf2 nuclear accumulation but inhibited Nrf2 binding to the AREs by approximate to 40% (P