title: Histone Methylation in Nickel-Smelting Industrial Workers.
abstract: BACKGROUND
  Nickel is an essential trace metal naturally found in the environment. It is also common in occupational settings, where it associates with various levels of both occupational and nonoccupational exposure In vitro studies have shown that nickel exposure can lead to intracellular accumulation of Ni2+, which has been associated with global decreases in DNA methylation, increases in chromatin condensation, reductions in H3K9me2, and elevated levels of H3K4me3. Histone modifications play an important role in modulating chromatin structure and gene expression. For example, tri-methylation of histone H3k4 has been found to be associated with transcriptional activation, and tri-methylation of H3k27 has been found to be associated with transcriptional repression. Aberrant histone modifications have been found to be associated with various human diseases, including cancer. The purpose of this work was to identify biomarkers for populations with occupational nickel exposure and to examine the relationship between histone methylation and nickel exposure. This may provide a scientific indicator of early health impairment and facilitate exploration of the molecular mechanism underlying cancer pathogenesis.
  
  
  METHODS
  One hundred and forty subjects with occupational exposure to Ni and 140 referents were recruited. H3K4 and H3K27 trimethylation levels were measured in subjects' blood cells.
  
  
  RESULTS
  H3K4me3 levels were found to be higher in nickel smelting workers (47.24±20.85) than in office workers (22.65±8.81; P = 0.000), while the opposite was found for levels of H3K27me3(nickel smelting workers, 13.88± 4.23; office workers, 20.67± 5.96; P = 0.000). H3K4me3 was positively (r = 0.267, P = 0.001) and H3K27 was negatively (r = -0.684, P = 0.000) associated with age and length of service in smelting workers.
  
  
  CONCLUSIONS
  This study indicated that occupational exposure to Ni is associated with alterations in levels of histone modification.
authors.affiliation: School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
authors.forename: Yana
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Workers' Hospital of Jinchuan Company, Jinchuan Group CO., LTD, Jinchang, Gansu, P.R. China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Pu
authors.affiliation: School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
authors.forename: Faxiang
authors.initials: F
authors.lastname: Gou
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: School of Public Health, Yale University, 60 College Street, New Haven, Connecticut, United States of America.
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.affiliation: School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China; College of Basic Medicine, Lanzhou University, Lanzhou, Gansu, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cheng
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D019175:DNA Methylation; D042421:Histone Code; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D009532:Nickel / Q000009:adverse effects*; D016273:Occupational Exposure / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006657:Histones; D009532:Nickel