 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 07, 2018 |
| Title |
Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
|
| Summary |
Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis
|
| |
|
| Overall design |
NGS data from purified alveolar epithelial type 2 (AT2) cells originating from 2 donor lungs, including whole genome bisulfite sequencing (WGBS) and Chromatin immunoprecipitation (ChIPseq)
|
| |
|
| Contributor(s) |
Stueve TR, Li WQ, Shi J, Marconett CN, Zhang T, Yang C, Mullen D, Wheeler W, Hua X, Zhou B, Borok Z, Caporaso N, Pesatori AC, Duan J, Laird-Offringa IA, Landi MT |
| Citation(s) |
28854564 |
| |
| Submission date |
Feb 16, 2017 |
| Last update date |
Jul 17, 2023 |
| Contact name |
Crystal N Marconett |
| E-mail(s) |
[email protected], [email protected]
|
| Phone |
626-218-4357
|
| Organization name |
City of Hope
|
| Department |
Integrative Translational Sciences
|
| Lab |
Crystal Marconett
|
| Street address |
1500 E Duarte Rd
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (8)
|
| GSM2493802 |
Donor1-WGBS library from purified primary AT2 cells |
| GSM2493803 |
Donor2-WGBS library from purified primary AT2 cells |
| GSM2493804 |
Donor 1- ChIPseq of H3K4me1 in purified primary AT2 cells |
| GSM2493805 |
Donor 2- ChIPseq of H3K4me1 in purified primary AT2 cells |
| GSM2493806 |
Donor 1- ChIPseq of H3K27Ac in purified primary AT2 cells |
| GSM2493807 |
Donor 2- ChIPseq of H3K27Ac in purified primary AT2 cells |
| GSM2493808 |
Donor 1- Input DNA that underwent reverse crosslinking from purified primary AT2 cells |
| GSM2493809 |
Donor 2- Input DNA that underwent reverse crosslinking from purified primary AT2 cells |
|
| Relations |
| BioProject |
PRJNA375086 |
| SRA |
SRP100067 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94986_RAW.tar |
2.7 Gb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...