CpG岛甲基化结合蛋白在氢醌致骨髓增殖性白血病病毒原癌基因转录激活中的作用

Epigenetic mechanism of MPL transcriptional activation induced by hydroquinone in TK6 cells

目的深入揭示氢醌（HQ）致MPL转录激活的表观遗传学机制。方法以磷酸盐缓冲液（PBS）溶解HQ，以正常TK6细胞、PBS处理细胞为对照组，分别以2．5、5．0、10．0和20．0μmol／LHQ染毒TK6细胞为染毒组。应用实时荧光定量一聚合酶链反应检测甲基化CpG结合蛋白1～5（MBD1～5）的表达。结果与对照细胞相比，MBD1—4的mRNA表达量在所有的HQ处理细胞中全部下降，20．0μmol／LHQ对MBD2和MBD4表达的抑制效果最为明显，抑制率分别为50％和32％（P〈O．05）；而10．0μmo1／LHQ对MBD1和MBD3表达的抑制效果最明显，抑制率分别为36％和33％（P〈0．05）；MBD5表达无统计学意义（P〉0．05）。在MPL的CpG岛内有3个MBD1序列特异性结合位点。结论HQ致MPL的转录激活可能与MBD1表达异常有关。

Objective To explore the epigenetie mechanism of MPL transcriptional activation induced by hydroquinone （HQ）. Methods HQ was dissolved with PBS buffer, 2.5, 5.0, 10.0 and 20.0μmol/L hydroquinone were given to TK6 cells, respectively, and the normal TK6 cells and cells treated with PBS were used as controls. Expressions of methyl-CpG-binding domain proteins 1-5 （MBD1-5） were tested by reverse transcription real-time RT-PCR assay. Results The expressions of MBD1-4 in the HQ-treated cells were decreased compared with those of the control cells and the expressions of MBD2 and MBD4 were severely inhibited by 20.0 μmol/L HQ , decreased by 50% and 32% （P〈0.05）, respectively, while the expressions of MBD1 and MBD3 were severely inhibited by 10.0 p, mol/L HQ, decreased by 36% and 33%（P〈0.05）. In CpG island of MPL, there were three sequence-specific biding sites for MBD1. Conclusion Transcriptional activation of MPL induced by HQ may be associated with the dysregulated expression of MBD1.