Skip to main content
SpringerLink
Log in

SWI/SNF Chromatin Remodeling Complex: A New Cofactor in Reprogramming

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Induced pluripotent stem (iPS) cells can be derived from somatic cells. Four key factors are required in this process including Oct4, Sox2, Klf4 and c-Myc. Ectopic expression of these four factors in somatic cells leads to reprogramming. Recent studies show that the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex plays critical roles in reprogramming of somatic cells and maintaining the pluripotency of stem cells. The possible mechanism is that SWI/SNF enhances the binding activity of reprogramming factors to pluripotent gene promoters and thus increases the reprogramming efficiency. Here, we review these recent advances and discuss how SWI/SNF plays a role in reprogramming. Understanding this mechanism will be helpful to find out the detail of reprogramming, which may provide a new therapy in medical science by generating patient-specific pluripotent stem cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kim, J. H., Auerbach, J. M., Rodríguez-Gómez, J. A., et al. (2002). Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature, 418, 50–56.

    Article  PubMed  CAS  Google Scholar 

  2. Liu, S., Qu, Y., Stewart, T. J., et al. (2000). Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proceedings of the National Academy of Sciences of the United States of America, 97, 6126–6131.

    Article  PubMed  CAS  Google Scholar 

  3. Zhang, F., & Pasumarthi, K. B. (2008). Embryonic stem cell transplantation promise and progress in the treatment of heart cisease. BioDrugs, 22, 361–374.

    Article  PubMed  CAS  Google Scholar 

  4. Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., & McKay, R. (2001). Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science, 292, 1389–1394.

    Article  PubMed  CAS  Google Scholar 

  5. Thomson, J., Itskovitz-Eldor, J., Shapiro, S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  6. Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., & Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature, 385, 810–813.

    Article  PubMed  CAS  Google Scholar 

  7. Cowan, C. A., Atienza, J., Melton, D. A., & Eggan, K. (2005). Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science, 309, 1369–1373.

    Article  PubMed  CAS  Google Scholar 

  8. Tada, M., Takahama, Y., Abe, K., Nakatsuji, N., & Tada, T. (2001). Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Current Biology, 11, 1553–1558.

    Article  PubMed  CAS  Google Scholar 

  9. Maherali, N., Sridharan, R., Xie, W., et al. (2007). Directly reprogrammed fibroblasts show global epigenetic remodelling and widespread tissue contribution. Cell Stem Cell, 1, 55–70.

    Article  PubMed  CAS  Google Scholar 

  10. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline competent induced pluripotent stem cells. Nature, 448, 313–317.

    Article  PubMed  CAS  Google Scholar 

  11. Wernig, M., Meissner, A., Foreman, R., et al. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES cell-like state. Nature, 448, 318–324.

    Article  PubMed  CAS  Google Scholar 

  12. Takahashi, K., Tanabe, K., & Ohnuki, M. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.

    Article  PubMed  CAS  Google Scholar 

  13. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.

    Article  PubMed  CAS  Google Scholar 

  14. Singhal, N., Graumann, J., Wu, G., et al. (2010). Chromatin-remodeling components of the BAF complex facilitate reprogramming. Cell, 141, 943–955.

    Article  PubMed  CAS  Google Scholar 

  15. Yu, J., Vodyanik, M., Smuga-Otto, K., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917–1920.

    Article  PubMed  CAS  Google Scholar 

  16. Markoulaki, S., Hanna, J., Beard, C., et al. (2009). Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nature Biotechnology, 27, 169–171.

    Article  PubMed  CAS  Google Scholar 

  17. Heng, J., Feng, B., Han, J., et al. (2010). The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent Cells. Cell Stem Cell, 6, 167–174.

    Article  PubMed  CAS  Google Scholar 

  18. Lyssiotis, C., Foreman, R., Staerk, J., et al. (2009). Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proceedings of the National Academy of Sciences of the United States of America, 106, 8912–8917.

    Article  PubMed  Google Scholar 

  19. Ichida, J., Blanchard, J., Lam, K., et al. (2009). A small-molecule inhibitor of Tgf-b signaling replaces Sox2 in reprogramming by inducing Nanog. Cell Stem Cell, 5, 491–503.

    Article  PubMed  CAS  Google Scholar 

  20. Yuan, X., Wan, H., Zhao, X., Zhu, S., Zhou, Q., & Ding, S. (2011). Brief report: Combined chemical treatment enables oct4-induced reprogramming from mouse embryonic fibroblasts. Stem Cells, 29, 549–553.

    Article  PubMed  CAS  Google Scholar 

  21. Picanço-Castro, V., Russo-Carbolante, E., Reis, L., et al. (2011). Pluripotent reprogramming of fibroblasts by lentiviralmediated insertion of SOX2, C-MYC, and TCL-1A. Stem Cells and Development, 20, 169–180.

    Article  PubMed  Google Scholar 

  22. Han, J., Yuan, P., Yang, H., et al. (2010). Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature, 463, 1096–1100.

    Article  PubMed  CAS  Google Scholar 

  23. Zhao, Y., Yin, X., Qin, H., et al. (2008). Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell, 3, 475–479.

    Article  PubMed  CAS  Google Scholar 

  24. Kim, J., Zaehres, H., Wu, G., et al. (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 454, 646–650.

    Article  PubMed  CAS  Google Scholar 

  25. Kim, J., Sebastiano, V., Wu, G., et al. (2009). Oct4-induced pluripotency in adult neural stem cells. Cell, 136, 411–419.

    Article  PubMed  CAS  Google Scholar 

  26. Kim, J., Greber, B., Araúzo-Bravo, M., et al. (2009). Direct reprogramming of human neural stem cells by OCT4. Nature, 461, 649–653.

    Article  PubMed  CAS  Google Scholar 

  27. Hanna, J., Markoulaki, S., Schorderet, P., et al. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133, 250–264.

    Article  PubMed  CAS  Google Scholar 

  28. Tomioka, I., Maeda, T., Shimada, H., et al. (2010). Generating induced pluripotent stem cells from common marmoset (Callithrix jacchus) fetal liver cells using defined factors, including Lin28. Genes to Cells, 15, 959–969.

    Article  PubMed  CAS  Google Scholar 

  29. Chambers, I., Colby, D., Robertson, M., et al. (2003). Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell, 113, 643–655.

    Article  PubMed  CAS  Google Scholar 

  30. Lavial, F., Acloque, H., Bertocchini, F., et al. (2007). The Oct4 homologue PouV and Nanog regulate pluripotency in chicken embryonic stem cells. Development, 134, 3549–3563.

    Article  PubMed  CAS  Google Scholar 

  31. Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., et al. (2003). The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell, 113, 631–642.

    Article  PubMed  CAS  Google Scholar 

  32. Yamaguchi, S., Kimura, H., Tada, M., et al. (2005). Nanog expression in mouse germ cell development. Gene Expression, 5, 639–646.

    Article  CAS  Google Scholar 

  33. Bhutani, N., Brady, J. J., Damian, M., Sacco, A., Corbel, S. Y., & Blau, H. M. (2010). Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature, 463, 1042–1047.

    Article  PubMed  CAS  Google Scholar 

  34. Silva, J., Nichols, J., Theunissen, T., et al. (2009). Nanog is the gateway to the pluripotent ground state. Cell, 138, 722–737.

    Article  PubMed  CAS  Google Scholar 

  35. Feng, B., Jiang, J., Kraus, P., et al. (2009). Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nature Cell Biology, 11, 197–203.

    Article  PubMed  CAS  Google Scholar 

  36. Imbalzano, A. N., Kwon, H., Green, M. R., & Kingston, R. E. (1994). Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature, 370, 481–485.

    Article  PubMed  CAS  Google Scholar 

  37. Kwon, H., Imbalzano, A. N., Khavari, P. A., Kingston, R. E., & Green, M. R. (1994). Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature, 370, 477–481.

    Article  PubMed  CAS  Google Scholar 

  38. Wang, W., Xue, Y., Zhou, S., Kuo, A., Cairns, B. R., & Crabtree, G. R. (1996). Diversity and specialization of mammalian SWI/SNF complexes. Genes & Development, 10, 2117–2130.

    Article  CAS  Google Scholar 

  39. Wang, G. G., Allis, C. D., & Chi, P. (2007a). Chromatin remodeling and cancer, part II: ATP-dependent chromatin remodeling. Trends in Molecular Medicine, 13, 373–380.

    Article  Google Scholar 

  40. Martens, J. A., & Winston, F. (2002). Evidence that Swi/Snf directly represses transcription in S. cerevisiae. Genes & Development, 16, 2231–2236.

    Article  CAS  Google Scholar 

  41. Batsché, E., Yaniv, M., & Muchardt, C. (2006). The human SWI/SNF subunit Brm is a regulator of alternative splicing. Nature Structural and Molecular Biology, 13, 22–29.

    Article  PubMed  Google Scholar 

  42. Becker, P. B., & Horz, W. (2002). ATP-dependent nucleosome modeling. Annual Review of Biochemistry, 71, 247–273.

    Article  PubMed  CAS  Google Scholar 

  43. Wang, G. G., Allis, C. D., & Chi, P. (2007b). Chromatin remodeling and cancer, part I: covalent histone modifications. Trends in Molecular Medicine, 13, 363–372.

    Article  CAS  Google Scholar 

  44. Gangaraju, V. K., & Bartholomew, B. (2007). Mechanisms of ATP dependent chromatin remodeling. Mutation Research, 618, 3–17.

    Article  PubMed  CAS  Google Scholar 

  45. Smith, C. L., Horowitz-Scherer, R., Flanagan, J. F., Woodcock, C. L., & Peterson, C. L. (2003). Structural analysis of the yeast SWI/SNF chromatin remodeling complex. Nature Structural Biology, 10, 141–145.

    Article  PubMed  CAS  Google Scholar 

  46. Monahan, B. J., Villén, J., Marguerat, S., Bähler, J., Gygi, S. P., & Winston, F. (2008). Yeast SWI/SNF and RSC complexes show compositional and functional differences from budding yeast. Nature Structural Biology, 15, 873–880.

    Article  CAS  Google Scholar 

  47. Du, J., Nasir, I., Benton, B. K., Kladde, M. P., & Laurent, B. C. (1998). Sth1p, a Saccharomyces cerevisiae Snf2p/Swi2p homolog, is an essential ATPase in RSC and differs from Snf/Swi in its interactions with histones and chromatin-associated proteins. Genetics, 150, 987–1005.

    PubMed  CAS  Google Scholar 

  48. Mohrmann, L., & Verrijzer, C. P. (2005). Composition and functional specificity of SWI2/SNF2 class chromatin remodeling complexes. Biochimica et Biophysica Acta, 1681, 59–73.

    PubMed  CAS  Google Scholar 

  49. Kadam, S., McAlpine, G. S., Phelan, M. L., Kingston, R. E., Jones, K. A., & Emerson, B. M. (2000). Functional selectivity of recombinant mammalian SWI/SNF subunits. Genes & Development, 14, 2441–2451.

    Article  CAS  Google Scholar 

  50. Yan, Z., Cui, K., Murray, D. M., et al. (2005). PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes. Genes & Development, 19, 1662–1667.

    Article  CAS  Google Scholar 

  51. Wang, W. (2003). The SWI/SNF family of ATP-dependent chromatin remodeler: similar mechanisms for diverse functions. Current Topics Microbiology and Immunology, 274, 143–169.

    Article  CAS  Google Scholar 

  52. Roberts, C. W., & Orkin, S. H. (2004). The SWI/SNF complex-chromatin and cancer. Nature Reviews Cancer, 4, 133–142.

    Article  PubMed  CAS  Google Scholar 

  53. Tang, L. L., Nogales, E., & Ciferri, C. (2010). Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcription. Progress in Biophysics and Molecular Biology, 102, 122–128.

    Article  PubMed  CAS  Google Scholar 

  54. Mak, A. B., Ni, Z., Hewel, J. A., et al. (2010). A lentiviral functional proteomics approach identifies chromatin remodeling complexes important for the induction of pluripotency. Molecular & Cellular Proteomics, 9, 811–823.

    Article  CAS  Google Scholar 

  55. Ho, L., Jothi, R., Ronan, J. L., Cui, K., Zhao, K., & Crabtree, G. R. (2009). An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network. Proceedings of the National Academy of Sciences of the United States of America, 106, 5187–5191.

    Article  PubMed  CAS  Google Scholar 

  56. Bultman, S. J., Gebuhr, T. C., Pan, H., & Svoboda, P. (2006). Maternal BRG1 regulates zygotic genome activation in the mouse. Genes & Development, 20, 1744–1754.

    Article  CAS  Google Scholar 

  57. Kidder, B. L., Palmer, S., & Knott, J. G. (2009). SWI/SNF-Brg1 regulates self-renewal and occupiescore pluripotency-related genes in embryonic stem cells. Stem Cells, 27, 317–328.

    Article  PubMed  CAS  Google Scholar 

  58. Yan, Z., Wang, Z., Sharova, L., et al. (2008). BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells. Stem Cells, 26, 1155–1165.

    Article  PubMed  CAS  Google Scholar 

  59. de la Serna, I. L., Ohkawa, Y., Higashi, C., et al. (2006). The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes. Journal of Biological Chemistry, 281, 20233–20241.

    Article  PubMed  Google Scholar 

  60. Young, D. W., Pratap, J., Javed, A., et al. (2005). SWI/SNF chromatin remodeling complex is obligatory for BMP2-induced, Runx2-dependent skeletal gene expression that controls osteoblast differentiation. Journal of Cellular Biochemistry, 94, 720–730.

    Article  PubMed  CAS  Google Scholar 

  61. Cheng, S. W., Davies, K. P., Yung, E., Beltran, R. J., Yu, J., & Kalpana, G. V. (1999). Beltran c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nature Genetics, 22, 102–105.

    Article  PubMed  CAS  Google Scholar 

  62. Singh, A. M., & Dalton, S. (2009). The cell cycle and Myc intersect with mechanisms that regulate pluripotency and reprogramming. Cell Stem Cell, 5, 141–149.

    Article  PubMed  CAS  Google Scholar 

  63. Inoue, H., Giannakopoulos, S., Parkhurst, C. N., et al. (2011). Target genes of the largest human SWI/SNF complex subunit control cell growth. Biochemical Journal, 434, 83–92.

    Article  PubMed  CAS  Google Scholar 

  64. Saladi, S. V., & de la Serna, I. L. (2010). ATP dependent chromatin remodeling enzymes in embryonic stem cells. Stem Cell Reviews, 6, 62–73.

    Article  PubMed  CAS  Google Scholar 

  65. Reisman, D., Glaros, S., & Thompson, E. A. (2009). The SWI/SNF complex and cancer. Oncogene, 28, 1653–1668.

    Article  PubMed  CAS  Google Scholar 

  66. Bultman, S., Gebuhr, T., Yee, D., et al. (2000). A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Molecular Cell, 6, 1287–1295.

    Article  PubMed  CAS  Google Scholar 

  67. Sridharan, R., Tchieu, J., Mason, M. J., et al. (2009). Role of the murine reprogramming factors in the induction of pluripotency. Cell, 136, 364–377.

    Article  PubMed  CAS  Google Scholar 

  68. Sims, H. I., Baughman, C. B., & Schnitzler, G. R. (2008). Human SWI/SNF directs sequence-specific chromatin changes on promoter polynucleosomes. Nucleic Acids Research, 36, 6118–6131.

    Article  PubMed  CAS  Google Scholar 

  69. Sims, H. I., Lane, J. M., Ulyanova, N. P., & Schnitzler, G. R. (2007). Human SWI/SNF drives sequence-directed repositioning of nucleosomes on c-Myc promoter DNA minicircles. Biochemistry, 46, 11377–11388.

    Article  PubMed  CAS  Google Scholar 

  70. Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. A., & Kosik, K. S. (2009). MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell, 137, 647–658.

    Article  PubMed  CAS  Google Scholar 

  71. Lin, S. L., Chang, D. C., Lin, C. H., Ying, S. Y., Leu, D., & Wu, D. T. (2011). Regulation of somatic cell reprogramming through inducible mir-302 expression. Nucleic Acids Research, 39, 1054–1065.

    Article  PubMed  CAS  Google Scholar 

  72. Yoo, A. S., Staahl, B. T., Chen, L., & Crabtree, G. R. (2009). MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature, 460, 642–646.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 30970701) and Natural Science Foundation Project of CQ CSTC (CSTC, 2010BB5072).

Conflict of Interest

The authors of this article declared they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China

    Ling He, Huan Liu & Liling Tang

Authors
  1. Ling He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liling Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liling Tang.

Additional information

Ling He and Huan Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, L., Liu, H. & Tang, L. SWI/SNF Chromatin Remodeling Complex: A New Cofactor in Reprogramming. Stem Cell Rev and Rep 8, 128–136 (2012). https://doi.org/10.1007/s12015-011-9285-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-011-9285-z

Keywords

Search

Navigation