Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target
Name
Jacks_Integrated cistromic.pdf
Size
1.06 MB
Format
Adobe PDF
Checksum (MD5)
7c7d233a0f9423f89d2d1efd04621469
Author(s)
Watanabe, Hideo
Francis, Joshua M.
Woo, Michele S.
Etemad, Banafsheh
Lin, Wenchu
Fries, Daniel F.
Peng, Shouyong
Snyder, Eric
Tata, Purushothama Rao
Izzo, Francesca
Date Issued
January 2013
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Watanabe, Hideo, Joshua M. Francis, Michele S. Woo, Banafsheh Etemad, Wenchu Lin, Daniel F. Fries, Shouyong Peng, et al. “Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target.” Genes & Development 27, no. 2 (January 24, 2013): 197-210.
Version
Final published version
Abstract
The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, 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. Integration of these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1. Further cistromic and overexpression analyses indicated that NKX2-1 can cooperate with the forkhead box transcription factor FOXA1 to regulate LMO3 gene expression. RNAi analysis of NKX2-1-amplified cells compared with nonamplified cells demonstrated that LMO3 mediates cell survival downstream from NKX2-1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transcriptional signal transducer in NKX2-1-amplified lung adenocarcinomas.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is available under a Creative Commons license; see publisher's site for details.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1101/gad.203208.112
