苯中毒病人 TOPO Ⅱα启动子调控因子 Sp1组蛋白化学修饰改变

摘要

AIM:To investigate the histone modification changes of topoisomerase Ⅱα( TOPOⅡα) promoter regulatory factor Sp1 in the patients with chronic benzene poisoning .METHODS:The bone marrow samples were collect-ed from 25 chronic benzene poisoning cases and 25 controls.The chromatin immunoprecipitation assay was carried out to study the possible mechanism of TOPOⅡαpromoter regulatory factor Sp 1 expression changes .The mRNA expression of Sp1 was detected by RT-PCR.RESULTS:Compared with the controls , the histone H4 acetylation and histone H3 acetyla-tion of Sp1 in the chronic benzene poisoning patients significantly decreased (P<0.01), and histone H3K9 methylation level of Sp1 increased (P<0.01), but the histone H3K4 methylation level of SP1 was not obviously changed (P>0.05). The mRNA expression of Sp1 in the chronic benzene poisoning patients was significantly lower than that in the controls (P<0.05).CONCLUSION:In chronic benzene poisoning patients , the histone acetylation and methylation modification changes of TOPOⅡαpromoter regulatory factor Sp 1 accompanied with the changes of mRNA level are observed .Histone H4 and H3 acetylation and H3K9 methylation modification of Sp1 may play an important role in the benzene ’s hematopoiet-ic toxicities.%目的：研究拓扑异构酶Ⅱα（ TOPOⅡα）启动子调控因子SP1组蛋白化学修饰在苯中毒病人中的改变。方法：25例临床慢性苯中毒患者骨髓单个核细胞为病例组，25例正常人骨髓单个核细胞为对照组，染色质免疫沉淀技术探讨TOPOⅡα启动子调控因子Sp1组蛋白乙酰化和甲基化水平的变化，RT－PCR法测定Sp1 mRNA的表达水平。结果：与对照组相比，临床苯中毒病例TOPOⅡα启动子调控因子Sp1组蛋白H4和H3乙酰化水平下降（P＜0．01），组蛋白H3K9甲基化水平升高（P＜0．01），组蛋白H3K4甲基化水平无明显改变。与正常对照组相比，临床苯中毒病例TOPOⅡα启动子调控因子Sp1的mRNA表达水平降低（ P＜0．05）。结论：慢性苯中毒TO－POⅡα启动子调控因子Sp1组蛋白H4、H3乙酰化及H3K9甲基化修饰水平的改变伴随着mRNA水平的变化。TOPOⅡα启动子调控因子Sp1可能通过组蛋白H4、H3乙酰化及H3K9甲基化修饰改变在苯中毒所致的造血毒性中发挥作用。