SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines
In: Oncogene, Jg. 25 (2005-10-26), Heft 3
Online
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Zugriff:
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.
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SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines
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Autor/in / Beteiligte Person: | Watanabe, Hirotaka ; Haraguchi, Takeshi ; Mizutani, Taketoshi ; Yamamichi-Nishina, Mitsue ; Sugiyama, Toshihiro ; Mori, Naoki ; Minoguchi, Shigeru ; Kameda, Takashi ; Iba, Hideo ; Yamamichi, Nobutake |
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Zeitschrift: | Oncogene, Jg. 25 (2005-10-26), Heft 3 |
Veröffentlichung: | 2005 |
Medientyp: | unknown |
ISSN: | 0950-9232 (print) |
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