Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development
文献类型：期刊论文
| 作者 | Chen, Yuting2; Teschendorff, Andrew E.2,3; Widschwendter, Martin3; Teschendorff, Andrew E.1; , |
| 刊名 | GENOME BIOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 18期号:-页码:236 |
| 关键词 | Smoking Cancer EWAS Transcription factor Regulatory network DNA methylation Gene expression Causality AHRR |
| ISSN号 | 1474-760X |
| DOI | 10.1186/s13059-017-1366-0 |
| 文献子类 | Article |
| 英文摘要 | Background: Diverse molecular alterations associated with smoking in normal and precursor lung cancer cells have been reported, yet their role in lung cancer etiology remains unclear. A prominent example is hypomethylation of the aryl hydrocarbon-receptor repressor (AHRR) locus, which is observed in blood and squamous epithelial cells of smokers, but not in lung cancer. Results: Using a novel systems-epigenomics algorithm, called SEPIRA, which leverages the power of a large RNA-sequencing expression compendium to infer regulatory activity from messenger RNA expression or DNA methylation (DNAm) profiles, we infer the landscape of binding activity of lung-specific transcription factors (TFs) in lung carcinogenesis. We show that lung-specific TFs become preferentially inactivated in lung cancer and precursor lung cancer lesions and further demonstrate that these results can be derived using only DNAm data. We identify subsets of TFs which become inactivated in precursor cells. Among these regulatory factors, we identify AHR, the aryl hydrocarbon-receptor which controls a healthy immune response in the lung epithelium and whose repressor, AHRR, has recently been implicated in smoking-mediated lung cancer. In addition, we identify FOXJ1, a TF which promotes growth of airway cilia and effective clearance of the lung airway epithelium from carcinogens. Conclusions: We identify TFs, such as AHR, which become inactivated in the earliest stages of lung cancer and which, unlike AHRR hypomethylation, are also inactivated in lung cancer itself. The novel systems-epigenomics algorithm SEPIRA will be useful to the wider epigenome-wide association study community as a means of inferring regulatory activity. |
| 学科主题 | Biotechnology & Applied Microbiology ; Genetics & Heredity |
| WOS关键词 | DNA METHYLATION CHANGES ; WIDE ASSOCIATION ; GENE-EXPRESSION ; MUTATIONAL PROCESSES ; F2RL3 METHYLATION ; TOBACCO SMOKING ; BLOOD DNA ; CELLS ; SIGNATURES ; LANDSCAPE |
| 语种 | 英语 |
| WOS记录号 | WOS:000418815900001 |
| 出版者 | BIOMED CENTRAL LTD |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/964]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.UCL, Canc Inst, Paul OGorman Bldg,72 Huntley St, London WC1E 6BT, England, 2.Chinese Acad Sci, MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 3.UCL, Dept Womens Canc, 74 Huntley St, London WC1E 6AU, England; |
| 推荐引用方式 GB/T 7714 | Chen, Yuting,Teschendorff, Andrew E.,Widschwendter, Martin,et al. Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development[J]. GENOME BIOLOGY,2017,18(-):236. |
| APA | Chen, Yuting,Teschendorff, Andrew E.,Widschwendter, Martin,Teschendorff, Andrew E.,&,.(2017).Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development.GENOME BIOLOGY,18(-),236. |
| MLA | Chen, Yuting,et al."Systems-epigenomics inference of transcription factor activity implicates aryl-hydrocarbon-receptor inactivation as a key event in lung cancer development".GENOME BIOLOGY 18.-(2017):236. |
入库方式： OAI收割
来源：上海营养与健康研究所
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