2006年1月
SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines
ONCOGENE
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- 巻
- 25
- 号
- 3
- 開始ページ
- 470
- 終了ページ
- 479
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/sj.onc.1209068
- 出版者・発行元
- NATURE PUBLISHING GROUP
Mammalian chromatin remodelingfact or, 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.
- リンク情報
- ID情報
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- DOI : 10.1038/sj.onc.1209068
- ISSN : 0950-9232
- PubMed ID : 16247481
- Web of Science ID : WOS:000234714100015