TOPO IIα启动子调控因子组蛋白甲基化修饰在苯中毒致造血毒性中的作用

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摘要目的：研究拓扑异构酶（TOPO）IIα启动子调控因子（SP1、ATF-2、SP3、NF-YA、NF-M、P53、C-MYB、C-JUN、ICBP90）组蛋白甲基化修饰在苯中毒致造血毒性中的作用。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，染色质免疫沉淀分析（ChIP）技术探讨TOPO IIα启动子各调控因子组蛋白甲基化水平的变化，RT-PCR法测定TOPO IIα启动子各调控因子mRNA表达水平的改变。结果：①与对照组比较，病例组TOPO IIα启动子调控因子NF-M、C-JUN组蛋白H3K4甲基化水平下降，差异有统计学意义（P＜0.05），SP1、ATF-2、SP3、NF-YA、P53、C-MYB、ICBP90组蛋白H3K4甲基化水平无明显改变（P＞0.05）；SP1、NF-M组蛋白H3K9甲基化水平升高，差异有统计学意义（P＜0.05或P＜0.01），而ATF-2、SP3、NF-YA、P53、C-MYB、C-JUN、ICBP90组白H3K9甲基化水平无明显改变（P＞0.05）。②与对照组比较，病例组TOPO IIα启动子调控因子SP1、NF-YA、C-MYB、NF-M及C-JUN mRNA表达水平降低，差异有统计学意义（P＜0.05或P＜0.01），ATF-2、ICBP90 mRNA表达水平不变（P＞0.05），SP3、P53 mRNA表达水平则升高（P＜0.05或P＜0.01）。结论：①慢性苯中毒TOPO IIα启动子调控因子组蛋白化学修饰水平的改变伴随着调控因子mRNA水平的变化。②TOPO IIα启动子调控因子组蛋白甲基化修饰在苯中毒所致的造血毒性中发挥一定的作用。

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	施益芬1
	郑周懿2
	陈晶晶2
	钱珊瑚2
	历嘉琪2
	俞康1

关键词 ：苯；拓扑异构酶II&alpha, 启动子调控因子；组蛋白甲基化；染色质免疫沉淀分析法

Abstract：Objective: To investigate histone methylation modification of topoisomerase IIα (TOPO IIα) promoter regulation factors in patients with chronic benzene poisoning, to explore the possible regulatory mechanism of TOPO IIα involved in toxicity of chronic benzene poisoning. Methods: The bone marrow samples were cellected
from 25 chronic benzene poisoning cases and 25 normal controls. The Chromatin Immunoprecipitation (ChIP) assay was carried out to study the possible mechanism of TOPO IIα promoter regulation factors expression changes.TOPO IIα promoter regulation factors mRNA were detected by RT-PCR technique. Results: Compared with the normal controls, the histone H3K4 methylation level of TOPO IIα promoter regulation factors NF-M, C-JUN in chronic benzene poisoning patients decreased (P<0.05), while the histone H3K4 methylation level of SP1, ATF-2, SP3, NF-YA, P53, C-MYB, ICBP90 without obvious change (P>0.05). The histone H3K9 methylation level of SP1, NF-M increased (P<0.05 or P<0.01), while the histone H3K9 methylation level of ATF-2, SP3, NF-YA, P53, C-MYB, C-JUN, ICBP90 was no significant change (P>0.05). The mRNA expression of TOPO IIα promoter regulation factors SP1, NF-YA, C-MYB, NF-M and C-JUN were significantly lower than that in the control (P<0.05 or P<0.01), while the expression of SP3, P53 mRNA increased (P<0.05 or P<0.01), ATF-2, ICBP90 mRNA wasn’t changed (P>0.05). Conclusion: In chronic benzene poisoning patients, TOPO IIα promoter regulation factors histone modification changes accompanied with mRNA level changed. Histone methylation modification of topoisomerase enzyme IIα promoter regulation factors play an important role in the benzene’s hematopoietic toxicities.

Key words： benzene topoisomerase II&alpha promoter regulation factors histone methylation ChIP

收稿日期: 2015-02-01

基金资助:国家自然科学基金资助项目（81172613）；温州市科技局科研基金资助项目（Y20120004，Y20090238）。

通讯作者: 俞康，教授，博士生导师，Email：yukang62@126.com。

作者简介: 施益芬（1981-），女，浙江永嘉人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2015/V45/I6/391

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