|
| Status |
Public on Jan 22, 2013 |
| Title |
NKX2-1 occupancy in human lung adenocarcinoma cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To better understand how genomic alterations of NKX2-1 drive tumorigenesis, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma, and analyzed DNA binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation from NKX2-1-amplified human lung adenocarcinoma cell lines. Combining these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1, in addition to consensus binding motifs including a nuclear hormone receptor signature and a Forkhead box motif in NKX2-1-bound sequences. RNA interference analysis of NKX2-1-amplified cells compared to non-amplified cells demonstrated that LMO3 mediates cell proliferation downstream of NKX2-1; cistromic analysis that NKX2-1 may cooperate with FOXA1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transducer of lineage specific cell survival of NKX2-1-amplified lung adenocarcinomas.
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| |
|
| Overall design |
NKX2-1 ChIP-seq from three lung adenocarcinoma cell lines with amplification of NKX2-1
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| |
|
| Contributor(s) |
Watanabe H |
| Citation(s) |
23322301 |
| |
| Submission date |
Aug 08, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Hideo Watanabe |
| E-mail(s) |
hideo.watanabe@mssm.edu
|
| Organization name |
Icahn School of Medicine at Mount Sinai
|
| Department |
Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine
|
| Lab |
Hideo Watanabe
|
| Street address |
One Gustave L. Levy Place
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA172254 |
| SRA |
SRP014763 |
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