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- Title
SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines.
- Authors
Watanabe, H.; Mizutani, T.; Haraguchi, T.; Yamamichi, N.; Minoguchi, S.; Yamamichi-Nishina, M.; Mori, N.; Kameda, T.; Sugiyama, T.; Iba, H.
- Abstract
Mammalian chromatin remodeling factor, SWI/SNF complex contains a single molecule of either Brm or BRG1 as the ATPase catalytic subunit. Here, we show that the SWI/SNF complex forms a larger complex with neuron-restrictive silencer factor (NRSF) and its corepressors, mSin3A and CoREST, in human nonsmall cell lung carcinoma cell lines. We also demonstrate that the strong transcriptional suppression of such neuron-specific genes as synaptophysin and SCG10 by NRSF in these non-neural cells requires the functional SWI/SNF complex; these neuronal genes were elevated in cell lines deficient in both Brm and BRG1, whereas retrovirus vectors expressing siRNAs targeting integral components of SWI/SNF complex (Brm/BRG1 or Ini1) induced expression of these neuronal genes in SWI/SNF-competent cell lines. In cell lines deficient in both Brm and BRG1, exogenous Brm or BRG1 suppressed expression of these neuronal genes in an ATP-dependent manner and induced efficient and specific deacetylation of histone H4 around the NRSF binding site present in the synaptophysin gene by a large complex containing the recruited functional SWI/SNF complex. Patients with Brm/BRG1-deficient lung carcinoma have been reported to carry poor prognosis; derepression of NRSF-regulated genes including these neuron-specific genes could contribute to enhance tumorigenicity and also would provide selective markers for Brm/BRG1-deficient tumors.Oncogene (2006) 25, 470–479. doi:10.1038/sj.onc.1209068; published online 10 October 2005
- Subjects
CHROMATIN; CATALYTIC RNA; IMMUNOSUPPRESSION; CANCER; HISTONE deacetylase; NEURONS; GENETIC regulation
- Publication
Oncogene, 2006, Vol 25, Issue 3, p470
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209068