Role of NSD1 in H2O2-induced GSTM3 suppression
Role of NSD1 in H2O2-induced GSTM3 suppression
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NSD1 在 H2O2 诱导的 GSTM3 抑制中的作用
DOI：
10.1016/j.cellsig.2014.08.026
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发表时间：
2014-12-01
影响因子：
4.8
通讯作者：
Zhao, Yanyan
中科院分区：
文献类型：
--
作者：
Chu, Guoming;Li, Yinghui;Zhao, Yanyan
核受体结合SET结构域蛋白1（NSD 1）是一种组蛋白甲基转移酶和转录辅助因子，参与基因表达调控。然而，NSD 1在氧化应激中的作用仍然知之甚少。在本研究中，我们集中在NSD 1的抗氧化酶基因谷胱甘肽S-转移酶M3（GSTM 3）的表达调控响应氧化应激。H2 O2处理导致NSD 1和GSTM 3的表达降低，并且通过特异性siRNA耗尽NSD 1的表达逆转H2 O2降低的GSTM 3表达。此外，我们还通过荧光素酶和体内、外DNA-蛋白结合试验研究了NSD 1对TATA盒附近GSTM 3启动子-63 A/C多态性的调控作用。GSTM 3启动子活性随NSD 1的过表达或缺失而升高或降低，但-63C不受影响。H_2O_2对GSTM 3启动子活性的抑制作用在-63A上大于-63C上，而NSD 1表达的缺失减弱了H_2O_2对-63A启动子的抑制作用，但增强了H_2O_2对-63C启动子的抑制作用。此外，NSD 1与RNAPII相互作用并结合GSTM 3 - 63 A/CTATA盒，与-63A的结合亲和力高于与-63C的结合亲和力。这些数据表明，NSD 1参与H2 O2诱导的氧化应激，H2 O2诱导的NSD 1抑制通过-63 A/C TATA盒导致GSTM 3表达减少。(C)2014爱思唯尔公司All rights reserved.
Nuclear receptor-binding SET domain-containing protein 1 (NSD1) has been proved to act as a histone methyltransferase and a transcription co-factor to regulate gene expression. However, the role of NSD1 in oxidative stress remains poorly understood. In the present study, we focused on the NSD1 regulation of antioxidant enzyme gene glutathione S-transferase M3 (GSTM3) expression in response to oxidative stress. H2O2 treatment caused the decrease of both NSD1 and GSTM3 expression, and the depletion of NSD1 expression by specific siRNA reversed the H2O2-reduced GSTM3 expression. Furthermore, we investigated NSD1 modulating the transcription of GSTM3 promoter with -63A/C polymorphism closed to TATA box in response to H2O2 by luciferase and in vitro or in vivo DNA-protein binding assays. The promoter activity of GSTM3 with -63A was higher than -63C, and was increased or decreased by the overexpression or depletion of NSD1, but -63C was not influenced. H2O2 repressed the promoter activity of GSTM3 with -63A more than -63C, and the depletion of NSD1 expression weakened H2O2 inhibition on the -63A promoter, but augmented H2O2 inhibition on the -63C promoter. In addition, NSD1 interacted with RNAPII and bound to GSTM3 -63A/C TATA box, with higher binding affinity to -63A than to -63C. These data indicated that NSD1 implicated in H2O2-induced oxidative stress, and H2O2-induced NSD1 suppression resulted in the decrease of GSTM3 expression through the -63A/C TATA box. (C) 2014 Elsevier Inc. All rights reserved.