title: Repression of Biotin-Related Proteins by Benzo[a]Pyrene-Induced Epigenetic Modifications in Human Bronchial Epithelial Cells.
abstract: Benzo[a]pyrene (B[a]P) exposure has been associated with the alteration in epigenetic marks that are involved in cancer development. Biotinidase (BTD) and holocarboxylase synthetase (HCS) are 2 major enzymes involved in maintaining the homeostasis of biotinylation, and the deregulation of this pathway has been associated with a number of cancers. However, the link between B[a]P exposure and the dysregulation of BTD/HCS in B[a]P-associated tumorigenesis is unknown. Here we showed that the expression of both BTD and HCS was significantly decreased upon B[a]P treatment in human bronchial epithelial (16HBE) cells. Benzo[a]pyrene exposure led to the global loss of DNA methylation by immunofluorescence, which coincided with the reduction in acetylation levels on histones H3 and H4 in 16HBE cells. Consistent with decreased histone acetylation, histone deacetylases (HDACs) HDAC2 and HDAC3 were significantly upregulated in a dosage-dependent manner. When DNA methylation or HDAC activity was inhibited, we found that the reduction in BTD and HCS was separately regulated through distinct epigenetic mechanisms. Together, our results suggested the potential link between B[a]P toxicity and deregulation of biotin homeostasis pathway in B[a]P-associated cancer development.
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China College of Food Science and Technology, Hunan Agricultural University, Changsha, Hunan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xia
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Lin-Qing
authors.initials: LQ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.affiliation: College of Horticulture and Gardening, Hunan Agricultural University, Changsha, Hunan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Xi-Fei
authors.initials: XF
authors.lastname: Yang
authors.affiliation: College of Food Science and Technology, Hunan Agricultural University, Changsha, Hunan, China.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Yi
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Xiao-Hu
authors.initials: XH
authors.lastname: Ren
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China junii8@126.com zxzhuang2007@sina.com.
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China junii8@126.com zxzhuang2007@sina.com.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001710:Biotin / Q000378:metabolism*; D043523:Biotinidase / Q000378:metabolism; D001980:Bronchi / Q000166:cytology; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000099186:Histone Deacetylase 3
chemical_list: D001564:Benzo(a)pyrene; D001710:Biotin; D043523:Biotinidase; D019731:Carbon-Nitrogen Ligases; D002273:Carcinogens; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D006657:Histones; D000099186:Histone Deacetylase 3; C533423:HDAC2 protein, human; C023312:holocarboxylase synthetases
keywords: DNA methylation; benzo[a]pyrene; biotinylation; histone acetylation