Association between Promoter Methylation of Gene ERCC3 and Benzene Hematotoxicity

Bibliographic Data

ID15480954
AuthorsZheng Min (0000-0002-8901-1050, National Institute for Occupational Health and Poison Control), Min Zheng (0000-0002-2337-8191, 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), Feiliang Lin (Chinese Academy of Sciences), Fenxia Hou (National Institute for Occupational Health and Poison Control), Guilan Li (0009-0000-6801-7747, National Institute for Occupational Health and Poison Control), Caiying Zhu (0000-0002-4521-7524, Chinese Academy of Medical Sciences & Peking Union Medical College), Peiyu Xu (0000-0003-3590-4037, Sichuan University), Caihong Xing (0000-0003-0625-3642, National Institute for Occupational Health and Poison Control, corresponding author), Qianfei Wang (0000-0002-6297-3954, Chinese Academy of Sciences, corresponding author)
Year2017
Volume14
Issue8
Pages921-921
Publication date2017-08-16
Open AccessYes
TypeARTICLE
VenueInternational Journal of Environmental Research and Public Health (JOURNAL)
Journal identifiersISSN: 1661-7827 • E-ISSN: 1660-4601
PublisherMultidisciplinary Digital Publishing Institute (PUBLISHER • CH)
DOI10.3390/ijerph14080921
PMID28813025
OpenAlexW2746742310
LanguageEN
Citations received4
References cited33

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

Association (psychology · Biology · DNA methylation · Gene · Gene expression · Methylation · Cancer-related gene regulation · Carcinogens and Genotoxicity Assessment · Epigenetics and DNA Methylation · Psychology · Genetics