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DOI | 10.1289/EHP1275 |
Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells | |
Chen, Danqi1; Fang, Lei1,6; Mei, Shenglin2; Li, Hongjie1,7; Xu, Xia1; Marais, Thomas L. Des1; Lu, Kun3; Liu, X. Shirley4,5; Jin, Chunyuan1 | |
2017-09-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
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ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文摘要 | BACKGROUND: Formaldehyde (FA) is an environmental and occupational chemical carcinogen. Recent studies have shown that exogenous FA causes only a modest increase in DNA adduct formation compared with the amount of adducts formed by endogenous FA, raising the possibility that epigenetic mechanisms may contribute to FA-mediated carcinogenicity. OBJECTIVES: We investigated the effects of FA exposure on histone modifications and chromatin assembly. We also examined the role of defective chromatin assembly in FA-mediated transcription and cell transformation. METHODS: Cellular fractionation and Western blot analysis were used to measure the levels of histone modifications in human bronchial epithelial BEAS-2B cells and human nasal RPM12650 cells in the presence of FA. Chromatin immunoprecipitation (ChIP) and micrococcal nuclease (MNase) digest assays were performed to examine the changes in chromatin assembly and accessibility after FA exposure. RNA sequencing (RNA-seq) and real-time polymerase chain reaction (PCR) were used to examine transcriptional dysregulation. Finally, anchorage-independent cell growth ability was tested by soft agar assay following FA exposure. RESULTS: Exposure to FA dramatically decreased the acetylation of the N-terminal tails of cytosolic histones. These modifications are important for histone nuclear import and subsequent chromatin assembly. Histone proteins were depleted in both the chromatin fraction and at most of the genomic loci tested following FA exposure, suggesting that FA compromises chromatin assembly. Moreover, FA increased chromatin accessibility and altered the expression of hundreds of cancer-related genes. Knockdown of the histone H3.3 gene (an H3 variant), which mimics inhibition of chromatin assembly, facilitated FA mediatedanchorage-independent cell growth. CONCLUSIONS: We propose that the inhibition of chromatin assembly represents a novel mechanism of cell transformation induced by he environmental and occupational chemical carcinogen FA. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000413792800029 |
WOS关键词 | HISTONE VARIANT H3.3 ; INHALED FORMALDEHYDE ; INHALATION EXPOSURE ; RHESUS-MONKEYS ; DNA-DAMAGE ; OCCUPATIONAL-EXPOSURE ; RESPIRATORY-TRACT ; MISMATCH REPAIR ; RISK-ASSESSMENT ; LEUKEMIA |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/24162 |
专题 | 资源环境科学 |
作者单位 | 1.NYU, Sch Med, Dept Environm Med & Biochem & Mol Pharmacol, New York, NY USA; 2.Tongji Univ, Sch Life Sci, Dept Bioinformat, Shanghai, Peoples R China; 3.Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA; 4.Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA; 5.Harvard TH Chan Sch Publ Hlth, Boston, MA USA; 6.Nanjing Univ, Med Sch, Nanjing, Jiangsu, Peoples R China; 7.Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA |
推荐引用方式 GB/T 7714 | Chen, Danqi,Fang, Lei,Mei, Shenglin,et al. Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(9). |
APA | Chen, Danqi.,Fang, Lei.,Mei, Shenglin.,Li, Hongjie.,Xu, Xia.,...&Jin, Chunyuan.(2017).Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells.ENVIRONMENTAL HEALTH PERSPECTIVES,125(9). |
MLA | Chen, Danqi,et al."Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells".ENVIRONMENTAL HEALTH PERSPECTIVES 125.9(2017). |
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