Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target
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 adenoca...
| Principais autores: | , , , , , , , , , , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | en_US |
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Cold Spring Harbor Laboratory Press
2014
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| Acesso em linha: | http://hdl.handle.net/1721.1/85103 https://orcid.org/0000-0001-5785-8911 |
| _version_ | 1826202242778136576 |
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| author | Watanabe, Hideo Francis, Joshua M. Woo, Michele S. Etemad, Banafsheh Lin, Wenchu Fries, Daniel F. Peng, Shouyong Snyder, Eric Tata, Purushothama Rao Izzo, Francesca Schinzel, Anna C. Cho, Jeonghee Hammerman, Peter S. Verhaak, Roel G. Hahn, William C. Rajagopal, Jayaraj Meyerson, Matthew L. Jacks, Tyler E |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Watanabe, Hideo Francis, Joshua M. Woo, Michele S. Etemad, Banafsheh Lin, Wenchu Fries, Daniel F. Peng, Shouyong Snyder, Eric Tata, Purushothama Rao Izzo, Francesca Schinzel, Anna C. Cho, Jeonghee Hammerman, Peter S. Verhaak, Roel G. Hahn, William C. Rajagopal, Jayaraj Meyerson, Matthew L. Jacks, Tyler E |
| author_sort | Watanabe, Hideo |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:04:45Z |
| format | Article |
| id | mit-1721.1/85103 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:04:45Z |
| publishDate | 2014 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/851032022-09-27T23:56:03Z Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target Watanabe, Hideo Francis, Joshua M. Woo, Michele S. Etemad, Banafsheh Lin, Wenchu Fries, Daniel F. Peng, Shouyong Snyder, Eric Tata, Purushothama Rao Izzo, Francesca Schinzel, Anna C. Cho, Jeonghee Hammerman, Peter S. Verhaak, Roel G. Hahn, William C. Rajagopal, Jayaraj Meyerson, Matthew L. Jacks, Tyler E Koch Institute for Integrative Cancer Research at MIT Snyder, Eric Jacks, Tyler E. 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. National Institutes of Health (U.S.) (NIH/NCI T32 Institutional Training Program fellowship (5T32CA009361-28)) National Cancer Institute (U.S.) (grant 5R01CA109038) National Cancer Institute (U.S.) (grant 5P20CA90578) 2014-02-26T20:38:19Z 2014-02-26T20:38:19Z 2013-01 2012-12 Article http://purl.org/eprint/type/JournalArticle 0890-9369 http://hdl.handle.net/1721.1/85103 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. https://orcid.org/0000-0001-5785-8911 en_US http://dx.doi.org/10.1101/gad.203208.112 Genes & Development Article is available under a Creative Commons license; see publisher's site for details. http://creativecommons.org/ application/pdf Cold Spring Harbor Laboratory Press Genes and Development |
| spellingShingle | Watanabe, Hideo Francis, Joshua M. Woo, Michele S. Etemad, Banafsheh Lin, Wenchu Fries, Daniel F. Peng, Shouyong Snyder, Eric Tata, Purushothama Rao Izzo, Francesca Schinzel, Anna C. Cho, Jeonghee Hammerman, Peter S. Verhaak, Roel G. Hahn, William C. Rajagopal, Jayaraj Meyerson, Matthew L. Jacks, Tyler E Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target |
| title | Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target |
| title_full | Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target |
| title_fullStr | Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target |
| title_full_unstemmed | Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target |
| title_short | Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target |
| title_sort | integrated cistromic and expression analysis of amplified nkx2 1 in lung adenocarcinoma identifies lmo3 as a functional transcriptional target |
| url | http://hdl.handle.net/1721.1/85103 https://orcid.org/0000-0001-5785-8911 |
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