Watanabe, HideoFrancis, Joshua M.Woo, Michele S.Etemad, BanafshehLin, WenchuFries, Daniel F.Peng, ShouyongSnyder, Eric L.Tata, Purushothama RaoIzzo, FrancescaSchinzel, Anna C.Cho, JeongheeHammerman, Peter S.Verhaak, Roel G.Hahn, William C.Rajagopal, JayarajJacks, TylerMeyerson, Matthew2019-10-132013Watanabe, H., J. M. Francis, M. S. Woo, B. Etemad, W. Lin, D. F. Fries, S. Peng, et al. 2013. “Integrated Cistromic and Expression Analysis of Amplified NKX2-1 in Lung Adenocarcinoma Identifies LMO3 as a Functional Transcriptional Target.” Genes & Development 27 (2): 197–210. doi:10.1101/gad.203208.112.0890-93691549-5477http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542747The 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.en-USJournal Article2019-10-1310.1101/gad.203208.112