In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 27, No. 2 ( 2013-01-15), p. 197-210
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0890-9369
,
1549-5477
DOI:
10.1101/gad.203208.112
Sprache:
Englisch
Verlag:
Cold Spring Harbor Laboratory
Publikationsdatum:
2013
ZDB Id:
1467414-2
SSG:
12
