CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

SMARCB1RDT; INI1; SNF5; Snr1; BAF47; MRD15; RTPS1; Sfh1p; hSNFS; SNF5L1

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

NA

Introduction

Full Name: SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 . SMARCB1 is a key component of the ATP-dependent SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex and is essential for SWI/SNF to perform its remodeling function both in vivo and in vitro. SMARCB1 is involved in proliferation, differentiation, transcriptional regulation, and tumor suppression (1-20).

Function and Interaction

SMARCB1 is indispensable for the viability and development of early embryonic cells, and SMARCB1 deletion can cause termination of development during the peri-implantation stage and embryonic lethality by embryonic day 7 (1-2). SMARCB1 is required for hepatocyte differentiation, and its deletion can result in serious hypoglycemia, neonatal death, and disrupted energetic metabolism and glycogen storage. SMARCB1 can impact the transcription of most of the genes that are thought to be upregulated during liver development, including genes associated with glycogen synthesis, gluconeogenesis, and cell-cell adhesion (3). SMARCB1 is also essential for adipocyte differentiation in murine 3T3-L1 preadipocytes and human mesenchymal stem cells, and it can interact with C/EBPbeta and PPARgamma2, thus regulating the expression of adipocyte-specific genes (4). SMARCB1 knockout causes cell-cycle arrest in G1, reduces the expression of both basal and stress-associated p53 in several human cell lines, and disrupts the p53-mediated transcription of p21 (5). SMARCB1 is related to glioma-associated oncogene family zinc finger-1 (GLI1), and its deletion can result in abnormal activation of the Hedgehog-Gli pathway (6).

Disease Association

SMARCB1 mutations are related to aggressive malignant rhabdoid tumors (MRT), which mostly occur in young children and are associated with a high lethality rate. It is found in the brain, kidneys, and soft tissues, indicating it to be a tumor suppressor (7-11). In addition, expression of SMARCB1 is lost in all renal medullary carcinomas, almost all epithelioid sarcomas, half of epithelioid malignant peripheral nerve sheath tumors, and some extraskeletal myxoid chondrosarcomas (12-18).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Homo sapiensHeLaEpitheliumCervixGSE24398 ,GSM601398
Click  DownloadNA21408204

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References

1. Klochendler-Yeivin, A., Fiette, L., Barra, J., Muchardt, C., Babinet, C. and Yaniv, M. (2000) The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression. Embo Rep, 1, 500-506.
2. Roberts, C.W.M., Galusha, S.A., McMenamin, M.E., Fletcher, C.D.M. and Orkin, S.H. (2000) Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. P Natl Acad Sci USA, 97, 13796-13800.
3. Gresh, L., Bourachot, B., Reimann, A., Guigas, B., Fiette, L., Garbay, S., Muchardt, C., Hue, L., Pontoglio, M., Yaniv, M. et al. (2005) The SWI/SNF chromatin-remodeling complex subunit SNF5 is essential for hepatocyte differentiation. Embo Journal, 24, 3313-3324.
4. Caramel, J., Medjkane, S., Quignon, F. and Delattre, O. (2008) The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors. Oncogene, 27, 2035-2044.
5. Xu, Y., Yan, W. and Chen, X. (2010) SNF5, a core component of the SWI/SNF complex, is necessary for p53 expression and cell survival, in part through eIF4E. Oncogene, 29, 4090-4100.
6. Jagani, Z., Mora-Blanco, E.L., Sansam, C.G., McKenna, E.S., Wilson, B., Chen, D.S., Klekota, J., Tamayo, P., Nguyen, P.T.L., Tolstorukov, M. et al. (2010) Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Nat Med, 16, 1429-U1112.
7. Versteege, I., Sevenet, N., Lange, J., Rousseau-Merck, M.F., Ambros, P., Handgretinger, R., Aurias, A. and Delattre, O. (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature, 394, 203-206.
8. Sevenet, N., Lellouch-Tubiana, A., Schofield, D., Khe, H.X., Gessler, M., Birnbaum, D., Jeanpierre, C., Jouvet, A. and Delattre, O. (1999) Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet, 8, 2359-2368.
9. Sevenet, N., Sheridan, E., Amram, D., Schneider, P., Handgretinger, R. and Delattre, O. (1999) Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet, 65, 1342-1348.
10. Roberts, C.W.M., Leroux, M.M., Fleming, M.D. and Orkin, S.H. (2002) Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell, 2, 415-425.
11. Roberts, C.W.M. and Orkin, S.H. (2004) The SWI/SNF complex - Chromatin and cancer. Nat Rev Cancer, 4, 133-142.
12. Oda, Y. and Tsuneyoshi, M. (2006) Extrarenal rhabdoid tumors of soft tissue: Clinicopathological and molecular genetic review and distinction from other soft-tissue sarcomas with rhabdoid features. Pathol Int, 56, 287-295.
13. Kohashi, K., Oda, Y., Yamamoto, H., Tamiya, S., Oshiro, Y., Izumi, T., Taguchi, T. and Tsuneyoshi, M. (2008) SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: A special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma. Am J Surg Pathol, 32, 1168-1174.
14. Kohashi, K., Izumi, T., Oda, Y., Yamamoto, H., Tamiya, S., Taguchi, T., Iwamoto, Y., Hasegawa, T. and Tsuneyoshi, M. (2009) Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Hum Pathol, 40, 349-355.
15. Cheng, J.X., Tretiakova, M., Gong, C., Mandal, S., Krausz, T. and Taxy, J.B. (2008) Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Modern Pathol, 21, 647-652.
16. Hornick, J.L., Dal Cin, P. and Fletcher, C.D.M. (2009) Loss of INI1 Expression is Characteristic of Both Conventional and Proximal-type Epithelioid Sarcoma. Am J Surg Pathol, 33, 542-550.
17. Hoot, A.C., Russo, P., Judkins, A.R., Perlman, E.J. and Biegel, J.A. (2004) Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors. Am J Surg Pathol, 28, 1485-1491.
18. Kohashi, K., Oda, Y., Yamamoto, H., Tamiya, S., Matono, H., Iwamoto, Y., Taguchi, T. and Tsuneyoshi, M. (2010) Reduced expression of SMARCB1/INI1 protein in synovial sarcoma. Modern Pathol, 23, 981-990.
19. Carlson, M. and Laurent, B.C. (1994) The Snf/Swi Family of Global Transcriptional Activators. Curr Opin Cell Biol, 6, 396-402.
20. Peterson, C.L. (1996) Multiple SWItches to turn on chromatin? Curr Opin Genet Dev, 6, 171-175.

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About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.