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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Andres ME, Burger C, Peral-Rubio MJ, Battaglioli E, Anderson ME, Grimes J et al. (1999). Proc Natl Acad Sci USA 96: 9873–9878.
Arai T, Takada M, Ui M, Iba H . (1999). Virology 260: 109–115.
Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME et al. (2001). Neuron 31: 353–365.
Battaglioli E, Andres ME, Rose DW, Chenoweth JG, Rosenfeld MG, Anderson ME et al. (2002). J Biol Chem 277: 41038–41045.
Borges M, Linnoila RI, van de Velde HJ, Chen H, Nelkin BD, Mabry M et al. (1997). Nature 386: 852–855.
Carnaghi C, Rimassa L, Garassino I, Santoro A . (2001). Ann Oncol 12 (Suppl 2): S119–S123.
Cheng SW, Davies KP, Yung E, Beltran RJ, Yu J, Kalpana GV . (1999). Nat Genet 22: 102–105.
Chiba H, Muramatsu M, Nomoto A, Kato H . (1994). Nucleic Acids Res 22: 1815–1820.
Chong JA, Tapia-Ramirez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC et al. (1995). Cell 80: 949–957.
Coulson JM, Edgson JL, Woll PJ, Quinn JP . (2000). Cancer Res 60: 1840–1844.
Fukuoka J, Fujii T, Shih JH, Dracheva T, Meerzaman D, Player A et al. (2004). Clin Cancer Res 10: 4314–4324.
Furumai R, Matsuyama A, Kobashi N, Lee KH, Nishiyama M, Nakajima H et al. (2002). Cancer Res 62: 4916–4921.
Grimes JA, Nielsen SJ, Battaglioli E, Miska EA, Speh JC, Berry DL et al. (2000). J Biol Chem 275: 9461–9467.
Gurrola-Diaz C, Lacroix J, Dihlmann S, Becker CM, von Knebel Doeberitz M . (2003). Oncogene 22: 5636–5645.
Huang Y, Myers SJ, Dingledine R . (1999). Nat Neurosci 2: 867–872.
Iba H, Mizutani T, Ito T . (2003). Rev Med Virol 13: 99–110.
Ito T, Yamauchi M, Nishina M, Yamamichi N, Mizutani T, Ui M et al. (2001). J Biol Chem 276: 2852–2857.
Khavari PA, Peterson CL, Tamkun JW, Mendel DB, Crabtree GR . (1993). Nature 366: 170–174.
Kowenz-Leutz E, Leutz A . (1999). Mol Cell 4: 735–743.
Lietz M, Hohl M, Thiel G . (2003). Eur J Biochem 270: 2–9.
Linnoila RI, Aisner SC . (1995). Lung Cancer. In: Johnson BE and Johnson DH (eds). New York: Wiley-Liss, pp. 73–95.
Linnoila RI . (1996). J Cell Biochem Suppl 24: 92–106.
Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J et al. (2002). Science 298: 1747–1752.
Martens JA, Winston F . (2002). Genes Dev 16: 2231–2236.
Martens JA, Winston F . (2003). Curr Opin Genet Dev 13: 136–142.
Mizutani T, Ito T, Nishina M, Yamamichi N, Watanabe A, Iba H . (2002). J Biol Chem 277: 15859–15864.
Mori N, Schoenherr C, Vandenbergh DJ, Anderson DJ . (1992). Neuron 9: 45–54.
Morita S, Kojima T, Kitamura T . (2000). Gene Therapy 7: 1063–1066.
Muchardt C, Yaniv M . (1993). EMBO J 12: 4279–4290.
Naruse Y, Aoki T, Kojima T, Mori N . (1999). Proc Natl Acad Sci USA 96: 13691–13696.
Niwa H, Yamamura K, Miyazaki J . (1991). Gene 108: 193–199.
Pal S, Yun R, Datta A, Lacomis L, Erdjument-Bromage H, Kumar J et al. (2003). Mol Cell Biol 23: 7475–7487.
Reisman DN, Sciarrotta J, Wang W, Funkhouser WK, Weissman BE . (2003). Cancer Res 63: 560–566.
Reisman DN, Strobeck MW, Betz BL, Sciariotta J, Funkhouser Jr W, Murchardt C et al. (2002). Oncogene 21: 1196–1207.
Roberts CW, Orkin SH . (2004). Nat Rev Cancer 4: 133–142.
Roopra A, Sharling L, Wood IC, Briggs T, Bachfischer U, Paquette AJ et al. (2000). Mol Cell Biol 20: 2147–2157.
Schoch S, Cibelli G, Thiel G . (1996). J Biol Chem 271: 3317–3323.
Schoenherr CJ, Anderson DJ . (1995). Science 267: 1360–1363.
Sif S, Saurin AJ, Imbalzano AN, Kingston RE . (2001). Genes Dev 15: 603–618.
Sudarsanam P, Winston F . (2000). Trends Genet 16: 345–351.
Tabuchi A, Yamada T, Sasagawa S, Naruse Y, Mori N, Tsuda M . (2002). Biochem Biophys Res Commun 290: 415–420.
Ui M, Takada M, Arai T, Matsumoto K, Yamada K, Nakahata T et al. (1999). Gene Therapy 6: 1670–1678.
Van Lommel A, Bolle T, Fannes W, Lauweryns JM . (1999). Arch Histol Cytol 62: 1–16.
Vanden Berghe W, De Bosscher K, Boone E, Plaisance S, Haegeman G . (1999). J Biol Chem 274: 32091–32098.
Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R et al. (1998). Nature 394: 203–206.
Wang W, Cote J, Xue Y, Zhou S, Khavari PA, Biggar SR et al. (1996). EMBO J 15: 5370–5382.
Westbrook TF, Martin ES, Schlabach MR, Leng Y, Liang AC, Feng B et al. (2005). Cell 121: 837–848.
Wong AK, Shanahan F, Chen Y, Lian L, Ha P, Hendricks K et al. (2000). Cancer Res 60: 6171–6177.
Yamamichi N, Yamamichi-Nishina M, Mizutani T, Watanabe H, Minoguchi S, Kobayashi N et al. (2005). Oncogene 24: 5471–5481.
Yamamichi-Nishina M, Ito T, Mizutani T, Yamamichi N, Watanabe H, Iba H . (2003). J Biol Chem 278: 7422–7430.
Yu JY, DeRuiter SL, Turner DL . (2002). Proc Natl Acad Sci USA 99: 6047–6052.
Acknowledgements
We thank Dr T Kitamura (Division of Cellular Therapy, IMS, University of Tokyo, Japan) for providing the PLAT packaging cell line and Dr T Ito for a critical reading of the manuscript. We also thank N Hashimoto and K Takeda for assistance in preparing this manuscript. Anti-Brm antibody was supplied by Kumamoto Immunochemical Laboratory, Transgenic Inc., Kumamoto, Japan. IMR-32 and 293 cell lines were obtained from the Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Japan. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, and Culture of Japan.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).
Supplementary information
Rights and permissions
About this article
Cite this article
Watanabe, H., Mizutani, T., Haraguchi, T. et al. SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines. Oncogene 25, 470–479 (2006). https://doi.org/10.1038/sj.onc.1209068
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209068
Keywords
This article is cited by
-
Author Correction: The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness of glioma initiating cells
Scientific Reports (2018)
-
Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition
BMC Cancer (2016)
-
Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation
Scientific Reports (2016)
-
The miR-199a/Brm/EGR1 axis is a determinant of anchorage-independent growth in epithelial tumor cell lines
Scientific Reports (2015)
-
Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity
Neuropsychopharmacology (2013)