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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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

Received: 01 February 2015

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	SHI Yifen1
	ZHENG Zhouyi2
	CHEN Jingjing2
	QIAN Shanhu2
	LI Jiaqi2
	YU Kang1.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2015/V45/I6/391

[1] Takahashi M, Tsujimura N, Yoshino T, et a1. Assessment of benzene-induced hematotoxicity using a human-like hematopoietic lineage in NOD/Shi-scid//IL-2Rγ null mice[J].PLOS One, 2012, 7(12): e50448.
[2] Lindsey RH, Bender RP, Osheroff N. Stimulation of topoisomerase II-mediated DNA cleavage by benzene metabolites[J]. Chem Biol Interact, 2005, 153-154: 197-205.
[3] Yu K, Shi YF, Yang KY, et a1. Decreased topoisomerase IIα expression and altered histone and regulatory factors of topoisomerase IIα promoter in patients with chronic benzene poisoning[J]. Toxicol Lett, 2011, 203(2): 111-117.
[4] 施益芬, 俞康, 陈怡, 等. 氢醌对人骨髓单个核细胞拓扑异构酶IIα表达的影响[J]. 中华劳动卫生职业病杂志, 2010, 28(9): 660-663.
[5] 施益芬, 俞康, 陈怡, 等. 氢醌对人骨髓单个核细胞拓扑异构酶IIα表达的影响及其可能机制[J]. 温州医学院学报,2010, 40(2): 164-167.
[6] Hampsey M, Reinberg D. Tails of intrigue: phosphorylation of RNA polymerase II mediates histone methylation[J]. Cell, 2003, 113(4): 429-432.
[7] Richards EJ, Elgin SC. Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects [J]. Cell, 2002, 108(4): 489-500.
[8] Magan N, Szremska AP, Isaacs RJ, et al. Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors[J]. Biochem J, 2003, 374(Pt 3): 723-729.
[9] Son MY, Kim TJ, Kweon KI, et al. ATF is important to late S phase-dependent regulation of DNA topoisomerase IIalpha gene expression in HeLa cells[J]. Cancer Lett, 2002, 184(1): 81-88.
[10] Hagen G, Müller S, Beato M, et al. Sp1-mediated transcription activation is repressed by Sp3[J]. EMBO J, 1994, 13 (16): 3843-3851.
[11] Joshi AA, Wu Z, Reed RF, et al. Nuclear factor-Y binding to the topoisomerase IIalpha promoter is inhibited by both the p53 tumor suppressor and anticancer drugs[J]. Mol Pharmacol, 2003, 63(2): 359-367.
[12] Brandt TL, Kroll DJ. NF-M trans-activates the human DNA topoisomerase II alpha promoter independently of c-Myb in HL-60 cells[J]. Leuk Res, 1997, 21(8): 711-720.
[13] Brandt TL, Fraser DJ, Leal S, et al. c-Myb trans-Activates the Human DNA Topoisomerase IIa Gene Promoter[J]. J Biol Chem, 1997, 272(10): 6278-6284.
[14] Wang Q, Zambetti GP, Suttle DP. Inhibition of DNA topoisomerase IIa gene expression by the p53 tumor suppressor [J]. Mol Cell Biol, 1997, 17(1): 389-397.
[15] Trotzier MA, Bronner C, Bathami K, et al. Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase IIalpha expression[J]. Biochem Biophys Res Commun, 2004, 319(2): 590-595.
[16] Kroll DJ, Sullivan DM, Gutierrez-Hartmann A. Modification of DNA topoisomerase II activity via direct interactions with the cyclic adenosine-3’, 5’-monophosphate response element-binding protein and related transcription factors[J]. Mol Endocrinol, 1993, 7(3): 305-318.