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Int. J. Environ. Res. Public Health 2017, 14(8), 921;

Association between Promoter Methylation of Gene ERCC3 and Benzene Hematotoxicity

Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital and Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China
Authors to whom correspondence should be addressed.
Received: 29 June 2017 / Revised: 21 July 2017 / Accepted: 24 July 2017 / Published: 16 August 2017
(This article belongs to the Section Environmental Health)
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Benzene is a primary industrial chemical and a ubiquitous environmental pollutant. ERCC3 is a key player in nucleotide excision repair. Recent studies suggested that site-specific methylation is a possible mechanism of the transcriptional dysregulation by blocking transcription factors binding. We previously found that the average promoter methylation level of ERCC3 was increased in benzene-exposed workers. In order to test whether specific CpG sites of ERCC3 play an important role in benzene-induced epigenetic changes and whether the specific methylation patterns are associated with benzene hematotoxicity, we analyzed the promoter methylation levels of individual CpG sites, transcription factor binding motif and the correlation between aberrant CpG methylation and hematotoxicity in 76 benzene-exposed workers and 24 unexposed controls in China. Out of all the CpGs analyzed, two CpG units located 43 bp upstream and 99 bp downstream of the transcription start site of ERCC3 (CpG 2–4 and CpG 17–18, respectively), showed the most pronounced increase in methylation levels in benzene-exposed workers, compared with unexposed controls (Mean ± SD: 5.86 ± 2.77% vs. 4.92 ± 1.53%, p = 0.032; 8.45 ± 4.09% vs. 6.79 ± 2.50%, p = 0.024, respectively). Using the JASPAR CORE Database, we found that CpG 2–4 and CpG 17–18 were bound by three putative transcription factors (TFAP2A, E2F4 and MZF1). Furthermore, the methylation levels for CpG 2–4 were correlated negatively with the percentage of neutrophils (β = −0.676, p = 0.005) in benzene-exposed workers. This study demonstrates that CpG-specific DNA methylation in the ERCC3 promoter region may be involved in benzene-induced epigenetic modification and it may contribute to benzene-induced hematotoxicity. View Full-Text
Keywords: benzene; occupational exposure; ERCC3; methylation; hematotoxicity benzene; occupational exposure; ERCC3; methylation; hematotoxicity

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Zheng, M.; Lin, F.; Hou, F.; Li, G.; Zhu, C.; Xu, P.; Xing, C.; Wang, Q. Association between Promoter Methylation of Gene ERCC3 and Benzene Hematotoxicity. Int. J. Environ. Res. Public Health 2017, 14, 921.

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