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PBRM1: A Critical Subunit of the SWI/SNF Chromatin Remodeling Complex

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Renal Cell Carcinoma

Abstract

Rapid advances in genomics have altered the landscape of oncology by accelerating the identification of disease-related oncogenes and tumor suppressors. It has become increasingly evident that even within specific cancer types there is incredible genetic diversity and heterogeneity, which may help explain the variability of responses to therapy. Greater understanding of these genetic changes will help the development of personalized, targeted care for patients. Large-scale sequencing projects, surveying whole exomes of clear cell renal cell carcinoma (ccRCC) tumors, have recently identified several important tumor suppressor genes, including PBRM1, SETD2, BAP1, and KDM5C. These genes are guiding new directions for oncology research and providing intriguing insights into ccRCC tumorigenesis. Specifically, the identification of these genes has heightened interest over discovering clinically useful kidney cancer biomarkers. Also, they have triggered intensive efforts in basic science laboratories to elucidate the biological function behind each enigmatic gene, with a view toward refining paradigms that more accurately reflect ccRCC formation and disease progression, and for developing better strategies for patient care.

This chapter summarizes the emerging information on these tumor suppressors, all of which appear to act as chromatin-modifying enzymes. We provide emphasis on the PBRM1 gene, identified as the most commonly mutated gene in ccRCC after the von Hippel-Lindau (VHL) tumor suppressor gene. We will also speculate on PBRM1’s ability to serve as a novel molecular target for therapy. For this purpose, we offer a description of nucleosome remodeling enzymes with attention focused on the SWI/SNF complexes, of which PBRM1 participates as an important accessory protein component.

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References

  1. Young AP, Schlisio S, Minamishima YA, et al. VHL loss actuates a HIF-independent senescence programme mediated by rb and p400. Nat Cell Biol. 2008;10(3):361–9.

    CAS  PubMed  Google Scholar 

  2. Hakimi AA, Chen YB, Wren J, et al. Clinical and pathologic impact of select chromatin-modulating tumor suppressors in clear cell renal cell carcinoma. Eur Urol. 2013;63(5):848–54.

    PubMed Central  PubMed  Google Scholar 

  3. Kovacs G, Erlandsson R, Boldog F, et al. Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci U S A. 1988;85(5):1571–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Varela I, Tarpey P, Raine K, et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011;469(7331):539–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nat Genet. 2012;44(7):751–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499(7456):43–9.

    Google Scholar 

  7. Duns G, Hofstra RM, Sietzema JG, et al. Targeted exome sequencing in clear cell renal cell carcinoma tumors suggests aberrant chromatin regulation as a crucial step in ccRCC development. Hum Mutat. 2012;33(7):1059–62.

    CAS  PubMed  Google Scholar 

  8. Hakimi AA, Ostrovnaya I, Reva B, et al. Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: A report by MSKCC and the KIRC TCGA research network. Clin Cancer Res. 2013;19(12):3259–67.

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Sato Y, Yoshizato T, Shiraishi Y, et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat Genet. 2013;45(8):860–7.

    CAS  PubMed  Google Scholar 

  10. Xia W, Nagase S, Montia AG, et al. BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer Res. 2008;68(6):1667–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Maitra A, Wistuba II, Washington C, et al. High-resolution chromosome 3p allelotyping of breast carcinomas and precursor lesions demonstrates frequent loss of heterozygosity and a discontinuous pattern of allele loss. Am J Pathol. 2001;159(1):119–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Wistuba II, Behrens C, Virmani AK, et al. High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res. 2000;60(7):1949–60.

    CAS  PubMed  Google Scholar 

  14. Sekine I, Sato M, Sunaga N, et al. The 3p21 candidate tumor suppressor gene BAF180 is normally expressed in human lung cancer. Oncogene. 2005;24(16):2735–8.

    CAS  PubMed  Google Scholar 

  15. Dalgliesh GL, Furge K, Greenman C, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature. 2010;463(7279):360–3.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13(3):153–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Ventii KH, Devi NS, Friedrich KL, et al. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res. 2008;68(17):6953–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Gokden N, Nappi O, Swanson PE, et al. Renal cell carcinoma with rhabdoid features. Am J Surg Pathol. 2000;24(10):1329–38.

    CAS  PubMed  Google Scholar 

  19. Kapur P, Pena-Llopis S, Christie A, et al. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol. 2013;14(2):159–67.

    CAS  PubMed  Google Scholar 

  20. Iwase S, Lan F, Bayliss P, et al. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 2007;128(6):1077–88.

    CAS  PubMed  Google Scholar 

  21. Niu X, Zhang T, Liao L, et al. The von hippel-lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C. Oncogene. 2012;31(6):776–86.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. de la Serna IL, Ohkawa Y, Imbalzano AN. Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nat Rev Genet. 2006;7(6):461–73.

    PubMed  Google Scholar 

  23. Boyer LA, Logie C, Bonte E, et al. Functional delineation of three groups of the ATP-dependent family of chromatin remodeling enzymes. J Biol Chem. 2000;275(25):18864–70.

    CAS  PubMed  Google Scholar 

  24. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem. 2009;78:273–304.

    CAS  PubMed  Google Scholar 

  25. Breeden L, Nasmyth K. Cell cycle control of the yeast HO gene: Cis- and trans-acting regulators. Cell. 1987;48(3):389–97.

    CAS  PubMed  Google Scholar 

  26. Stern M, Jensen R, Herskowitz I. Five SWI genes are required for expression of the HO gene in yeast. J Mol Biol. 1984;178(4):853–68.

    CAS  PubMed  Google Scholar 

  27. Neigeborn L, Carlson M. Genes affecting the regulation of SUC2 gene expression by glucose repression in saccharomyces cerevisiae. Genetics. 1984;108(4):845–58.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Phelan ML, Sif S, Narlikar GJ, Kingston RE. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell. 1999;3(2):247–53.

    CAS  PubMed  Google Scholar 

  29. Tamkun JW, Deuring R, Scott MP, et al. Brahma: a regulator of drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell. 1992;68(3):561–72.

    CAS  PubMed  Google Scholar 

  30. Khavari PA, Peterson CL, Tamkun JW, Mendel DB, Crabtree GR. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature. 1993;366(6451):170–4.

    CAS  PubMed  Google Scholar 

  31. Reyes JC, Barra J, Muchardt C, Camus A, Babinet C, Yaniv M. Altered control of cellular proliferation in the absence of mammalian brahma (SNF2alpha). EMBO J. 1998;17(23):6979–91.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Bultman S, Gebuhr T, Yee D, et al. A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol Cell. 2000;6(6):1287–95.

    CAS  PubMed  Google Scholar 

  33. Shen H, Powers N, Saini N, et al. The SWI/SNF ATPase brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 2008;68(24):10154–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Marshall TW, Link KA, Petre-Draviam CE, Knudsen KE. Differential requirement of SWI/SNF for androgen receptor activity. J Biol Chem. 2003;278(33):30605–13.

    CAS  PubMed  Google Scholar 

  35. Klokk TI, Kurys P, Elbi C, et al. Ligand-specific dynamics of the androgen receptor at its response element in living cells. Mol Cell Biol. 2007;27(5):1823–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Sun A, Tawfik O, Gayed B, et al. Aberrant expression of SWI/SNF catalytic subunits BRG1/BRM is associated with tumor development and increased invasiveness in prostate cancers. Prostate. 2007;67(2):203–13.

    CAS  PubMed  Google Scholar 

  37. Wong AK, Shanahan F, Chen Y, et al. BRG1, a component of the SWI-SNF complex, is mutated in multiple human tumor cell lines. Cancer Res. 2000;60(21):6171–7.

    CAS  PubMed  Google Scholar 

  38. Bultman SJ, Herschkowitz JI, Godfrey V, et al. Characterization of mammary tumors from Brg1 heterozygous mice. Oncogene. 2008;27(4):460–8.

    CAS  PubMed  Google Scholar 

  39. Bochar DA, Wang L, Beniya H, et al. BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer. Cell. 2000;102(2):257–65.

    CAS  PubMed  Google Scholar 

  40. Medina PP, Carretero J, Fraga MF, Esteller M, Sidransky D, Sanchez-Cespedes M. Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors. Genes Chromosomes Cancer. 2004;41(2):170–7.

    CAS  PubMed  Google Scholar 

  41. Reisman DN, Sciarrotta J, Wang W, Funkhouser WK, Weissman BE. Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis. Cancer Res. 2003;63(3):560–6.

    CAS  PubMed  Google Scholar 

  42. Glaros S, Cirrincione GM, Palanca A, Metzger D, Reisman D. Targeted knockout of BRG1 potentiates lung cancer development. Cancer Res. 2008;68(10):3689–96.

    CAS  PubMed  Google Scholar 

  43. Bourgo RJ, Siddiqui H, Fox S, et al. SWI/SNF deficiency results in aberrant chromatin organization, mitotic failure, and diminished proliferative capacity. Mol Biol Cell. 2009;20(14):3192–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Muchardt C, Bourachot B, Reyes JC, Yaniv M. Ras transformation is associated with decreased expression of the brm/SNF2alpha ATPase from the mammalian SWI-SNF complex. EMBO J. 1998;17(1):223–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Strober BE, Dunaief JL, Guha S, Goff SP. Functional interactions between the hBRM/hBRG1 transcriptional activators and the pRB family of proteins. Mol Cell Biol. 1996;16(4):1576–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Glaros S, Cirrincione GM, Muchardt C, Kleer CG, Michael CW, Reisman D. The reversible epigenetic silencing of BRM: Implications for clinical targeted therapy. Oncogene. 2007;26(49):7058–66.

    CAS  PubMed  Google Scholar 

  47. Liu G, Gramling S, Munoz D, et al. Two novel BRM insertion promoter sequence variants are associated with loss of BRM expression and lung cancer risk. Oncogene. 2011;30(29):3295–304.

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Gramling S, Rogers C, Liu G, Reisman D. Pharmacologic reversal of epigenetic silencing of the anticancer protein BRM: a novel targeted treatment strategy. Oncogene. 2011;30(29):3289–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Kalpana GV, Marmon S, Wang W, Crabtree GR, Goff SP. Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. Science. 1994;266(5193):2002–6.

    CAS  PubMed  Google Scholar 

  50. Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999;59(1):74–9.

    CAS  PubMed  Google Scholar 

  51. Roberts CW, Galusha SA, McMenamin ME, Fletcher CD, Orkin SH. Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci U S A. 2000;97(25):13796–800.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Roberts CW, Leroux MM, Fleming MD, Orkin SH. Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell. 2002;2(5):415–25.

    CAS  PubMed  Google Scholar 

  53. McKenna ES, Sansam CG, Cho YJ, et al. Loss of the epigenetic tumor suppressor SNF5 leads to cancer without genomic instability. Mol Cell Biol. 2008;28(20):6223–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Lee RS, Stewart C, Carter SL, et al. A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. J Clin Invest. 2012;122(8):2983–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Doan DN, Veal TM, Yan Z, Wang W, Jones SN, Imbalzano AN. Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes. Oncogene. 2004;23(19):3462–73.

    CAS  PubMed  Google Scholar 

  56. Wang X, Sansam CG, Thom CS, et al. Oncogenesis caused by loss of the SNF5 tumor suppressor is dependent on activity of BRG1, the ATPase of the SWI/SNF chromatin remodeling complex. Cancer Res. 2009;69(20):8094–101.

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Wilson BG, Wang X, Shen X, et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell. 2010;18(4):316–28.

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Mora-Blanco EL, Mishina Y, Tillman EJ, et al. Activation of beta-catenin/TCF targets following loss of the tumor suppressor SNF5. Oncogene. 2013. doi:10/1038/onc.2013.37.

    Google Scholar 

  59. Jagani Z, Mora-Blanco EL, Sansam CG, et al. Loss of the tumor suppressor Snf5 leads to aberrant activation of the hedgehog-gli pathway. Nat Med. 2010;16(12):1429–33.

    CAS  PubMed  Google Scholar 

  60. Jiang J, Hui CC. Hedgehog signaling in development and cancer. Dev Cell. 2008;15(6):801–12.

    CAS  PubMed  Google Scholar 

  61. Ruiz i Altaba A, Mas C, Stecca B. The gli code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol. 2007;17(9):438–47.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Wang W, Xue Y, Zhou S, Kuo A, Cairns BR, Crabtree GR. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 1996;10(17):2117–30.

    CAS  PubMed  Google Scholar 

  63. Chen J, Archer TK. Regulating SWI/SNF subunit levels via protein-protein interactions and proteasomal degradation: BAF155 and BAF170 limit expression of BAF57. Mol Cell Biol. 2005;25(20):9016–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Keppler BR, Archer TK. Ubiquitin-dependent and ubiquitin-independent control of subunit stoichiometry in the SWI/SNF complex. J Biol Chem. 2010;285(46):35665–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Sohn DH, Lee KY, Lee C, et al. SRG3 interacts directly with the major components of the SWI/SNF chromatin remodeling complex and protects them from proteasomal degradation. J Biol Chem. 2007;282(14):10614–24.

    CAS  PubMed  Google Scholar 

  66. Lee KY, Choi YI, Kim J, et al. Down-regulation of the SWI/SNF chromatin remodeling activity by TCR signaling is required for proper thymocyte maturation. J Immunol. 2007;178(11):7088–96.

    CAS  PubMed  Google Scholar 

  67. DelBove J, Rosson G, Strobeck M, et al. Identification of a core member of the SWI/SNF complex, BAF155/SMARCC1, as a human tumor suppressor gene. Epigenetics. 2011;6(12):1444–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Andersen CL, Christensen LL, Thorsen K, et al. Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer. Br J Cancer. 2009;100(3):511–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Shadeo A, Chari R, Lonergan KM, et al. Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia. BMC Genomics. 2008;9:64-2164-9-64.

    Google Scholar 

  70. Heeboll S, Borre M, Ottosen PD, et al. SMARCC1 expression is upregulated in prostate cancer and positively correlated with tumour recurrence and dedifferentiation. Histol Histopathol. 2008;23(9):1069–76.

    CAS  PubMed  Google Scholar 

  71. Jones S, Wang TL, Shih I, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010;330(6001):228–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Wiegand KC, Shah SP, Al-Agha OM, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010;363(16):1532–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Guan B, Mao TL, Panuganti PK, et al. Mutation and loss of expression of ARID1A in uterine low-grade endometrioid carcinoma. Am J Surg Pathol. 2011;35(5):625–32.

    PubMed Central  PubMed  Google Scholar 

  74. Lichner Z, Scorilas A, White NM, et al. The chromatin remodeling gene ARID1A is a new prognostic marker in clear cell renal cell carcinoma. Am J Pathol. 2013;182(4):1163–70.

    CAS  PubMed  Google Scholar 

  75. Wang X, Nagl Jr NG, Flowers S, Zweitzig D, Dallas PB, Moran E. Expression of p270 (ARID1A), a component of human SWI/SNF complexes, in human tumors. Int J Cancer. 2004;112(4):636.

    CAS  PubMed  Google Scholar 

  76. Mamo A, Cavallone L, Tuzmen S, et al. An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer. Oncogene. 2012;31(16):2090–100.

    CAS  PubMed  Google Scholar 

  77. Wang DD, Chen YB, Pan K, et al. Decreased expression of the ARID1A gene is associated with poor prognosis in primary gastric cancer. PLoS One. 2012;7(7):e40364.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Wang K, Kan J, Yuen ST, et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet. 2011;43(12):1219–23.

    CAS  PubMed  Google Scholar 

  79. Zang ZJ, Cutcutache I, Poon SL, et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 2012;44(5):570–4.

    CAS  PubMed  Google Scholar 

  80. Gui Y, Guo G, Huang Y, et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet. 2011;43(9):875–8.

    CAS  PubMed  Google Scholar 

  81. Imielinski M, Berger AH, Hammerman PS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012;150(6):1107–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Giulino-Roth L, Wang K, MacDonald TY, et al. Targeted genomic sequencing of pediatric burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes. Blood. 2012;120(26):5181–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Sausen M, Leary RJ, Jones S, et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat Genet. 2013;45(1):12–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Streppel MM, Lata S, Delabastide M, et al. Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in barrett's esophagus. Oncogene. 2013;33(3):347–57.

    PubMed Central  PubMed  Google Scholar 

  85. Shain AH, Giacomini CP, Matsukuma K, et al. Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer. Proc Natl Acad Sci U S A. 2012;109(5):E252–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Huang J, Deng Q, Wang Q, et al. Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma. Nat Genet. 2012;44(10):1117–21.

    CAS  PubMed  Google Scholar 

  87. Guichard C, Amaddeo G, Imbeaud S, et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 2012;44(6):694–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Li M, Zhao H, Zhang X, et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet. 2011;43(9):828–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Guan B, Wang TL, Shih I. ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer Res. 2011;71(21):6718–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Burrows AE, Smogorzewska A, Elledge SJ. Polybromo-associated BRG1-associated factor components BRD7 and BAF180 are critical regulators of p53 required for induction of replicative senescence. Proc Natl Acad Sci U S A. 2010;107(32):14280–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Drost J, Mantovani F, Tocco F, et al. BRD7 is a candidate tumour suppressor gene required for p53 function. Nat Cell Biol. 2010;12(4):380–9.

    CAS  PubMed  Google Scholar 

  92. Oh J, Sohn DH, Ko M, Chung H, Jeon SH, Seong RH. BAF60a interacts with p53 to recruit the SWI/SNF complex. J Biol Chem. 2008;283(18):11924–34.

    CAS  PubMed  Google Scholar 

  93. Xue Y, Canman JC, Lee CS, et al. The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes. Proc Natl Acad Sci U S A. 2000;97(24):13015–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Oliver AW, Jones SA, Roe SM, Matthews S, Goodwin GH, Pearl LH. Crystal structure of the proximal BAH domain of the polybromo protein. Biochem J. 2005;389(Pt 3):657–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Wang Z, Zhai W, Richardson JA, et al. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation. Genes Dev. 2004;18(24):3106–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Huang X, Gao X, Diaz-Trelles R, Ruiz-Lozano P, Wang Z. Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180. Dev Biol. 2008;319(2):258–66.

    CAS  PubMed  Google Scholar 

  97. Yan Z, Cui K, Murray DM, et al. PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes. Genes Dev. 2005;19(14):1662–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Tsurusaki Y, Okamoto N, Ohashi H, et al. Mutations affecting components of the SWI/SNF complex cause coffin-siris syndrome. Nat Genet. 2012;44(4):376–8.

    CAS  PubMed  Google Scholar 

  99. Santen GW, Aten E, Sun Y, et al. Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause coffin-siris syndrome. Nat Genet. 2012;44(4):379–80.

    CAS  PubMed  Google Scholar 

  100. Nie Z, Xue Y, Yang D, et al. A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex. Mol Cell Biol. 2000;20(23):8879–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Dallas PB, Cheney IW, Liao DW, et al. p300/CREB binding protein-related protein p270 is a component of mammalian SWI/SNF complexes. Mol Cell Biol. 1998;18(6):3596–603.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Gao X, Tate P, Hu P, Tjian R, Skarnes WC, Wang Z. ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a. Proc Natl Acad Sci U S A. 2008;105(18):6656–61.

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Krosl J, Mamo A, Chagraoui J, et al. A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations. Blood. 2010;116(10):1678–84.

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Trotter KW, Fan HY, Ivey ML, Kingston RE, Archer TK. The HSA domain of BRG1 mediates critical interactions required for glucocorticoid receptor-dependent transcriptional activation in vivo. Mol Cell Biol. 2008;28(4):1413–26.

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Chandler RL, Brennan J, Schisler JC, Serber D, Patterson C, Magnuson T. ARID1a-DNA interactions are required for promoter occupancy by SWI/SNF. Mol Cell Biol. 2013;33(2):265–80.

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Trotter KW, Archer TK. Reconstitution of glucocorticoid receptor-dependent transcription in vivo. Mol Cell Biol. 2004;24(8):3347–58.

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Wang X, Nagl NG, Wilsker D, et al. Two related ARID family proteins are alternative subunits of human SWI/SNF complexes. Biochem J. 2004;383(Pt 2):319–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Kaeser MD, Aslanian A, Dong MQ, Yates III JR, Emerson BM. BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells. J Biol Chem. 2008;283(47):32254–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Li XS, Trojer P, Matsumura T, Treisman JE, Tanese N. Mammalian SWI/SNF – a subunit BAF250/ARID1 is an E3 ubiquitin ligase that targets histone H2B. Mol Cell Biol. 2010;30(7):1673–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Sanchez R, Zhou MM. The role of human bromodomains in chromatin biology and gene transcription. Curr Opin Drug Discov Devel. 2009;12(5):659–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer. 2012;12(7):465–77.

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Middeljans E, Wan X, Jansen PW, Sharma V, Stunnenberg HG, Logie C. SS18 together with animal-specific factors defines human BAF-type SWI/SNF complexes. PLoS One. 2012;7(3):e33834.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Kzhyshkowska J, Rusch A, Wolf H, Dobner T. Regulation of transcription by the heterogeneous nuclear ribonucleoprotein E1B-AP5 is mediated by complex formation with the novel bromodomain-containing protein BRD7. Biochem J. 2003;371(Pt 2):385–93.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Harte MT, O'Brien GJ, Ryan NM, et al. BRD7, a subunit of SWI/SNF complexes, binds directly to BRCA1 and regulates BRCA1-dependent transcription. Cancer Res. 2010;70(6):2538–47.

    CAS  PubMed  Google Scholar 

  115. Kim S, Lee J, Park J, Chung J. BP75, bromodomain-containing M(r) 75,000 protein, binds dishevelled-1 and enhances wnt signaling by inactivating glycogen synthase kinase-3 beta. Cancer Res. 2003;63(16):4792–5.

    CAS  PubMed  Google Scholar 

  116. Wang W, Chi T, Xue Y, Zhou S, Kuo A, Crabtree GR. Architectural DNA binding by a high-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes. Proc Natl Acad Sci U S A. 1998;95(2):492–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Chi TH, Wan M, Zhao K, et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature. 2002;418(6894):195–9.

    CAS  PubMed  Google Scholar 

  118. Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell. 1995;83(6):835–9.

    CAS  PubMed  Google Scholar 

  119. Hsiao PW, Deroo BJ, Archer TK. Chromatin remodeling and tissue-selective responses of nuclear hormone receptors. Biochem Cell Biol. 2002;80(3):343–51.

    CAS  PubMed  Google Scholar 

  120. Garcia-Pedrero JM, Kiskinis E, Parker MG, Belandia B. The SWI/SNF chromatin remodeling subunit BAF57 is a critical regulator of estrogen receptor function in breast cancer cells. J Biol Chem. 2006;281(32):22656–64.

    CAS  PubMed  Google Scholar 

  121. Link KA, Burd CJ, Williams E, et al. BAF57 governs androgen receptor action and androgen-dependent proliferation through SWI/SNF. Mol Cell Biol. 2005;25(6):2200–15.

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Reisman DN, Sciarrotta J, Bouldin TW, Weissman BE, Funkhouser WK. The expression of the SWI/SNF ATPase subunits BRG1 and BRM in normal human tissues. Appl Immunohistochem Mol Morphol. 2005;13(1):66–74.

    CAS  PubMed  Google Scholar 

  123. Hsiao PW, Fryer CJ, Trotter KW, Wang W, Archer TK. BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Mol Cell Biol. 2003;23(17):6210–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Lai D, Wan M, Wu J, et al. Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling. Proc Natl Acad Sci U S A. 2009;106(4):1169–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Faralli H, Martin E, Core N, et al. Teashirt-3, a novel regulator of muscle differentiation, associates with BRG1-associated factor 57 (BAF57) to inhibit myogenin gene expression. J Biol Chem. 2011;286(26):23498–510.

    CAS  PubMed Central  PubMed  Google Scholar 

  126. Caubit X, Lye CM, Martin E, et al. Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4. Development. 2008;135(19):3301–10.

    CAS  PubMed  Google Scholar 

  127. Hah N, Kolkman A, Ruhl DD, et al. A role for BAF57 in cell cycle-dependent transcriptional regulation by the SWI/SNF chromatin remodeling complex. Cancer Res. 2010;70(11):4402–11.

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Link KA, Balasubramaniam S, Sharma A, et al. Targeting the BAF57 SWI/SNF subunit in prostate cancer: a novel platform to control androgen receptor activity. Cancer Res. 2008;68(12):4551–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Chestkov AV, Baka ID, Kost MV, Georgiev GP, Buchman VL. The d4 gene family in the human genome. Genomics. 1996;36(1):174–7.

    CAS  PubMed  Google Scholar 

  130. Zeng L, Zhang Q, Li S, Plotnikov AN, Walsh MJ, Zhou MM. Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b. Nature. 2010;466(7303):258–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Matsuyama R, Takada I, Yokoyama A, et al. Double PHD fingers protein DPF2 recognizes acetylated histones and suppresses the function of estrogen-related receptor alpha through histone deacetylase 1. J Biol Chem. 2010;285(24):18166–76.

    CAS  PubMed Central  PubMed  Google Scholar 

  132. Lange M, Kaynak B, Forster UB, et al. Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex. Genes Dev. 2008;22(17):2370–84.

    CAS  PubMed Central  PubMed  Google Scholar 

  133. Lessard J, Wu JI, Ranish JA, et al. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron. 2007;55(2):201–15.

    CAS  PubMed Central  PubMed  Google Scholar 

  134. Ghosh S, May MJ, Kopp EB. NF-kappa B and rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225–60.

    CAS  PubMed  Google Scholar 

  135. Ishizaka A, Mizutani T, Kobayashi K, et al. Double plant homeodomain (PHD) finger proteins DPF3a and -3b are required as transcriptional co-activators in SWI/SNF complex-dependent activation of NF-kappaB RelA/p50 heterodimer. J Biol Chem. 2012;287(15):11924–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Tando T, Ishizaka A, Watanabe H, et al. Requiem protein links RelB/p52 and the brm-type SWI/SNF complex in a noncanonical NF-kappaB pathway. J Biol Chem. 2010;285(29):21951–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Pomerantz JL, Baltimore D. Two pathways to NF-kappaB. Mol Cell. 2002;10(4):693–5.

    CAS  PubMed  Google Scholar 

  138. Giguere V, Yang N, Segui P, Evans RM. Identification of a new class of steroid hormone receptors. Nature. 1988;331(6151):91–4.

    CAS  PubMed  Google Scholar 

  139. Giguere V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev. 2008;29(6):677–96.

    CAS  PubMed  Google Scholar 

  140. Chen EI, Hewel J, Krueger JS, et al. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res. 2007;67(4):1472–86.

    CAS  PubMed  Google Scholar 

  141. Ao A, Wang H, Kamarajugadda S, Lu J. Involvement of estrogen-related receptors in transcriptional response to hypoxia and growth of solid tumors. Proc Natl Acad Sci U S A. 2008;105(22):7821–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Krasteva V, Buscarlet M, Diaz-Tellez A, Bernard MA, Crabtree GR, Lessard JA. The BAF53a subunit of SWI/SNF-like BAF complexes is essential for hemopoietic stem cell function. Blood. 2012;120(24):4720–32.

    CAS  PubMed  Google Scholar 

  143. Bao X, Tang J, Lopez-Pajares V, et al. ACTL6a enforces the epidermal progenitor state by suppressing SWI/SNF-dependent induction of KLF4. Cell Stem Cell. 2013;12(2):193–203.

    CAS  PubMed Central  PubMed  Google Scholar 

  144. Nishimoto N, Watanabe M, Watanabe S, et al. Heterocomplex formation by Arp4 and beta-actin is involved in the integrity of the Brg1 chromatin remodeling complex. J Cell Sci. 2012;125(Pt 16):3870–82.

    CAS  PubMed  Google Scholar 

  145. Olave I, Wang W, Xue Y, Kuo A, Crabtree GR. Identification of a polymorphic, neuron-specific chromatin remodeling complex. Genes Dev. 2002;16(19):2509–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Yoo AS, Staahl BT, Chen L, Crabtree GR. MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature. 2009;460(7255):642–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  147. Yoo AS, Sun AX, Li L, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 2011;476(7359):228–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Wu JI, Lessard J, Olave IA, et al. Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron. 2007;56(1):94–108.

    CAS  PubMed  Google Scholar 

  149. Aizawa H, Hu SC, Bobb K, et al. Dendrite development regulated by CREST, a calcium-regulated transcriptional activator. Science. 2004;303(5655):197–202.

    CAS  PubMed  Google Scholar 

  150. Ho L, Ronan JL, Wu J, et al. An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proc Natl Acad Sci U S A. 2009;106(13):5181–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  151. Lickert H, Takeuchi JK, Von Both I, et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature. 2004;432(7013):107–12.

    CAS  PubMed  Google Scholar 

  152. Debril MB, Gelman L, Fayard E, Annicotte JS, Rocchi S, Auwerx J. Transcription factors and nuclear receptors interact with the SWI/SNF complex through the BAF60c subunit. J Biol Chem. 2004;279(16):16677–86.

    CAS  PubMed  Google Scholar 

  153. Ito T, Yamauchi M, Nishina M, et al. Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers. J Biol Chem. 2001;276(4):2852–7.

    CAS  PubMed  Google Scholar 

  154. Vega RB, Huss JM, Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol. 2000;20(5):1868–76.

    CAS  PubMed Central  PubMed  Google Scholar 

  155. Li S, Liu C, Li N, et al. Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. Cell Metab. 2008;8(2):105–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  156. Li W, Bengtson MH, Ulbrich A, et al. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One. 2008;3(1):e1487.

    PubMed Central  PubMed  Google Scholar 

  157. Forcales SV, Albini S, Giordani L, et al. Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex. EMBO J. 2011;31(2):301–16.

    PubMed Central  PubMed  Google Scholar 

  158. Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007;109(1):31–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  159. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  160. Zuber J, Shi J, Wang E, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  161. Mertz JA, Conery AR, Bryant BM, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011;108(40):16669–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  162. Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy to target c-myc. Cell. 2011;146(6):904–17.

    CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Chung-Han Lee M.D., Ph.D.

  2. Human Oncology and Pathogenesis Program, Kettering Cancer Center, New York, NY, USA

    Can G. Pham Ph.D.

  3. Department of Human Oncology Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY, 10065, USA

    James J. Hsieh M.D., Ph.D.

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  1. Chung-Han Lee M.D., Ph.D.
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  2. Can G. Pham Ph.D.
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  3. James J. Hsieh M.D., Ph.D.
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Correspondence to James J. Hsieh M.D., Ph.D. .

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  1. Taussig Cancer Center, Cleveland Clinic, Pepper Pike, Ohio, USA

    Ronald M. Bukowski

  2. Division of Hematology Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Robert A. Figlin

  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Robert J. Motzer

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Lee, CH., Pham, C.G., Hsieh, J.J. (2015). PBRM1: A Critical Subunit of the SWI/SNF Chromatin Remodeling Complex. In: Bukowski, R., Figlin, R., Motzer, R. (eds) Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1622-1_5

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