Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP2395 |
Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type Specific Enhancer Activation and Gene Expression | |
Wan, Ma1; Bennett, Brian D.2; Pittman, Gary S.1; Campbell, Michelle R.1; Reynolds, Lindsay M.3; Porter, Devin K.1; Growl, Christopher L.1; Wang, Xuting1; Su, Dan1; Englert, Neal A.1; Thompson, Isabel J.1; Liu, Yongmei3; Bell, Douglas A.1 | |
2018-04-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES |
ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2018 |
卷号 | 126期号:4 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | BACKGROUND: Cigarette smoke is a causal factor in cancers and cardiovascular disease. Smoking-associated differentially methylated regions (SMDMRs) have been observed in disease studies, but the causal link between altered DNA methylation and transcriptional change is obscure. OBJECTIVE: Our objectives were to finely resolve SM-DMRs and to interrogate the mechanistic link between SM-DMRs and altered transcription of enhancer noncoding RNA (eRNA) and mRNA in human circulating monocytes. METHOD: We integrated SM-DMRs identified by reduced representation bisullite sequencing (RRBS) of circulating CD14 + monocyte DNA collected from two independent human studies [n = 38 from Clinical Research Unit (CRU) and n = 55 from the Multi-Ethnic Study of Atherosclerosis (MESA), about half of whom were active smokers] with gene expression for protein-coding genes and noncoding RNAs measured by RT-PCR or RNA sequencing. Candidate SM-DMRs were compared with RRBS of purified CD4 + T cells, CD8 + T cells, CD15 + granulocytes, CD19 + B cells, and CD56 + NK cells (n = 19 females, CRU). DMRs were validated using pyrosequencing or bisullite amplicon sequencing in up to 85 CRU volunteers, who also provided saliva DNA. RESULTS: RRBS identified monocyte SM-DMRs frequently located in putative gene regulatory regions. The most significant monocyte DMR occurred at a poised enhancer in the aryl-hydrocarbon receptor repressor gene (AHRR) and it was also detected in both granulocytes and saliva DNA. To our knowledge, we identify for the first time that SM-DMRs in or near AIIRR, C.5aff.55-EXOC-AS, and SASH/were associated with increased noncoding eRNA as well as mRNA in monocytes. Functionally, the AHRR SM-DMR appeared to up-regulate AHRR mRNA through activating the AHRR enhancer, as suggested by increased eRNA in the monocytes, but not granulocytes, from smokers compared with nonsmokers. CONCLUSIONS: Our findings suggest that AHRR SM-DMR up-regulates AHRR mRNA in a monocyte-specific manner by activating the AHRR enhancer. Cell type specific activation of enhancers at SM-DMRs may represent a mechanism driving smoking-related disease. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000431396900008 |
WOS关键词 | HYDROCARBON RECEPTOR REPRESSOR ; DNA-METHYLATION ; CIGARETTE-SMOKING ; HUMAN MONOCYTES ; EPIGENETIC MODIFICATIONS ; CARDIOVASCULAR-DISEASE ; WIDE ASSOCIATION ; MATERNAL SMOKING ; HUMAN GENOME ; ATHEROSCLEROSIS |
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/22454 |
专题 | 资源环境科学 |
作者单位 | 1.NIEHS, Environm Epigen & Dis Grp, Immun Inflammat & Dis Lab, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA; 2.NIEHS, Integrat Bioinformat Support Grp, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA; 3.Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA |
推荐引用方式 GB/T 7714 | Wan, Ma,Bennett, Brian D.,Pittman, Gary S.,et al. Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type Specific Enhancer Activation and Gene Expression[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2018,126(4). |
APA | Wan, Ma.,Bennett, Brian D..,Pittman, Gary S..,Campbell, Michelle R..,Reynolds, Lindsay M..,...&Bell, Douglas A..(2018).Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type Specific Enhancer Activation and Gene Expression.ENVIRONMENTAL HEALTH PERSPECTIVES,126(4). |
MLA | Wan, Ma,et al."Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type Specific Enhancer Activation and Gene Expression".ENVIRONMENTAL HEALTH PERSPECTIVES 126.4(2018). |
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