Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Setdb1 Is Required for Myogenic Differentiation of C2C12 Myoblast Cells via Maintenance of MyoD Expression

  • Song, Young Joon (Department of Biological Sciences, College of Natural Science, Inha University) ;
  • Choi, Jang Hyun (Department of Biological Sciences, College of Natural Science, Inha University) ;
  • Lee, Hansol (Department of Biological Sciences, College of Natural Science, Inha University)
  • Received : 2014.11.03
  • Accepted : 2014.12.15
  • Published : 2015.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Setdb1, an H3-K9 specific histone methyltransferase, is associated with transcriptional silencing of euchromatic genes through chromatin modification. Functions of Setdb1 during development have been extensively studied in embryonic and mesenchymal stem cells as well as neurogenic progenitor cells. But the role of Sedtdb1 in myogenic differentiation remains unknown. In this study, we report that Setdb1 is required for myogenic potential of C2C12 myoblast cells through maintaining the expressions of MyoD and muscle-specific genes. We find that reduced Setdb1 expression in C2C12 myoblast cells severely delayed differentiation of C2C12 myoblast cells, whereas exogenous Setdb1 expression had little effect on. Gene expression profiling analysis using oligonucleotide microarray and RNA-Seq technologies demonstrated that depletion of Setdb1 results in downregulation of MyoD as well as the components of muscle fiber in proliferating C2C12 cells. In addition, exogenous expression of MyoD reversed transcriptional repression of MyoD promoter-driven luciferase reporter by Setdb1 shRNA and rescued myogenic differentiation of C2C12 myoblast cells depleted of endogenous Setdb1. Taken together, these results provide new insights into how levels of key myogenic regulators are maintained prior to induction of differentiation.

Keywords

References

  1. Bilodeau, S., Kagey, M.H., Frampton, G.M., Rahl, P.B., and Young, R.A. (2009). SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev. 23, 2484-2489. https://doi.org/10.1101/gad.1837309
  2. Blais, A., Tsikitis, M., Acosta-Alvear, D., Sharan, R., Kluger, Y., and Dynlacht, B.D. (2005). An initial blueprint for myogenic differentiation. Genes Dev. 19, 553-569. https://doi.org/10.1101/gad.1281105
  3. Blum, R., and Dynlacht, B.D. (2013). The role of MyoD1 and histone modifications in the activation of muscle enhancers. Epigenetics 8, 778-784. https://doi.org/10.4161/epi.25441
  4. Cao, Y., Kumar, R.M., Penn, B.H., Berkes, C.A., Kooperberg, C., Boyer, L.A., Young, R.A., and Tapscott, S.J. (2006). Global and gene-specific analyses show distinct roles for Myod and Myog at a common set of promoters. EMBO J. 25, 502-511. https://doi.org/10.1038/sj.emboj.7600958
  5. Caretti, G., Di Padova, M., Micales, B., Lyons, G.E., and Sartorelli, V. (2004). The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev. 18, 2627-2638. https://doi.org/10.1101/gad.1241904
  6. Chen, C.M., Kraut, N., Groudine, M., and Weintraub, H. (1996). I-mf, a novel myogenic repressor, interacts with members of the MyoD family. Cell 86, 731-741. https://doi.org/10.1016/S0092-8674(00)80148-8
  7. Choi, J., Jang, H., Kim, H., Lee, J.H., Kim, S.T., Cho, E.J., and Youn, H.D. (2014). Modulation of lysine methylation in myocyte enhancer factor 2 during skeletal muscle cell differentiation. Nucleic Acids Res. 42, 224-234. https://doi.org/10.1093/nar/gkt873
  8. Delgado, I., Huang, X., Jones, S., Zhang, L., Hatcher, R., Gao, B., and Zhang, P. (2003). Dynamic gene expression during the onset of myoblast differentiation in vitro. Genomics 82, 109-121. https://doi.org/10.1016/S0888-7543(03)00104-6
  9. Dilworth, F.J., Seaver, K.J., Fishburn, A.L., Htet, S.L., and Tapscott, S.J. (2004). In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation. Proc. Natl. Acad. Sci. USA 101, 11593-11598. https://doi.org/10.1073/pnas.0404192101
  10. Dodge, J.E., Kang, Y.K., Beppu, H., Lei, H., and Li, E. (2004). Histone H3-K9 methyltransferase ESET is essential for early development. Mol. Cell. Biol. 24, 2478-2486. https://doi.org/10.1128/MCB.24.6.2478-2486.2004
  11. Eom, G.H., Kim, K.B., Kim, J.H., Kim, J.Y., Kim, J.R., Kee, H.J., Kim, D.W., Choe, N., Park, H.J., Son, H.J., et al. (2011). Histone methyltransferase SETD3 regulates muscle differentiation. J. Biol. Chem. 286, 34733-34742. https://doi.org/10.1074/jbc.M110.203307
  12. Hasty, P., Bradley, A., Morris, J.H., Edmondson, D.G., Venuti, J.M., Olson, E.N., and Klein, W.H. (1993). Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature 364, 501-506. https://doi.org/10.1038/364501a0
  13. Jen, Y., Weintraub, H., and Benezra, R. (1992). Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins. Genes Dev 6, 1466-1479. https://doi.org/10.1101/gad.6.8.1466
  14. Lassar, A.B., Davis, R.L., Wright, W.E., Kadesch, T., Murre, C., Voronova, A., Baltimore, D., and Weintraub, H. (1991). Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell 66, 305-315. https://doi.org/10.1016/0092-8674(91)90620-E
  15. Lee, H., Habas, R., and Abate-Shen, C. (2004). MSX1 cooperates with histone H1b for inhibition of transcription and myogenesis. Science 304, 1675-1678. https://doi.org/10.1126/science.1098096
  16. Ling, B.M., Bharathy, N., Chung, T.K., Kok, W.K., Li, S., Tan, Y.H., Rao, V.K., Gopinadhan, S., Sartorelli, V., Walsh, M.J., et al. (2012). Lysine methyltransferase G9a methylates the transcription factor MyoD and regulates skeletal muscle differentiation. Proc. Natl. Acad. Sci. USA 109, 841-846. https://doi.org/10.1073/pnas.1111628109
  17. Mal, A.K. (2006). Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation. EMBO J. 25, 3323-3334. https://doi.org/10.1038/sj.emboj.7601229
  18. Mal, A., and Harter, M.L. (2003). MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis. Proc. Natl. Acad. Sci. USA 100, 1735-1739. https://doi.org/10.1073/pnas.0437843100
  19. Mal, A., Sturniolo, M., Schiltz, R.L., Ghosh, M.K., and Harter, M.L. (2001). A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program. EMBO J. 20, 1739-1753. https://doi.org/10.1093/emboj/20.7.1739
  20. Mitchell, P.O., Mills, T., O'Connor, R.S., Kline, E.R., Graubert, T., Dzierzak, E., and Pavlath, G.K. (2005). Sca-1 negatively regulates proliferation and differentiation of muscle cells. Dev. Biol. 283, 240-252. https://doi.org/10.1016/j.ydbio.2005.04.016
  21. Molkentin, J.D., Black, B.L., Martin, J.F., and Olson, E.N. (1995). Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell 83, 1125-1136. https://doi.org/10.1016/0092-8674(95)90139-6
  22. Moran, J.L., Li, Y., Hill, A.A., Mounts, W.M., and Miller, C.P. (2002). Gene expression changes during mouse skeletal myoblast differentiation revealed by transcriptional profiling. Physiol. Genomics 10, 103-111. https://doi.org/10.1152/physiolgenomics.00011.2002
  23. Puri, P.L., Avantaggiati, M.L., Balsano, C., Sang, N., Graessmann, A., Giordano, A., and Levrero, M. (1997a). p300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription. EMBO J. 16, 369-383. https://doi.org/10.1093/emboj/16.2.369
  24. Puri, P.L., Sartorelli, V., Yang. X.J., Hamamori. Y., Ogryzko. V.V., Howard. B.H., Kedes. L., Wang. J.Y., Graessmann. A., Nakatani. Y., and Levrero, M. (1997b). Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. Mol. Cell 1 35-45. https://doi.org/10.1016/S1097-2765(00)80005-2
  25. Rao, S.S., and Kohtz, D.S. (1995). Positive and negative regulation of D-type cyclin expression in skeletal myoblasts by basic fibroblast growth factor and transforming growth factor beta. A role for cyclin D1 in control of myoblast differentiation. J. Biol. Chem. 270, 4093-4100. https://doi.org/10.1074/jbc.270.8.4093
  26. Rudnicki, M.A., Schnegelsberg, P.N., Stead, R.H., Braun, T., Arnold, H.H., and Jaenisch, R. (1993). MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75, 1351-1359. https://doi.org/10.1016/0092-8674(93)90621-V
  27. Sabourin, L.A., and Rudnicki, M.A. (2000). The molecular regulation of myogenesis. Clin. Genet. 57, 16-25.
  28. Sartorelli, V., and Caretti, G. (2005). Mechanisms underlying the transcriptional regulation of skeletal myogenesis. Curr. Opin. Genet. Dev. 15, 528-535. https://doi.org/10.1016/j.gde.2005.04.015
  29. Sartorelli, V., and Juan, A.H. (2011). Sculpting chromatin beyond the double helix: epigenetic control of skeletal myogenesis. Curr. Top. Dev. Biol. 96, 57-83. https://doi.org/10.1016/B978-0-12-385940-2.00003-6
  30. Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G., and Rauscher, F.J., 3rd (2002). SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 16, 919-932. https://doi.org/10.1101/gad.973302
  31. Seenundun, S., Rampalli, S., Liu, Q.C., Aziz, A., Palii, C., Hong, S., Blais, A., Brand, M., Ge, K., and Dilworth, F.J. (2010). UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO J. 29, 1401-1411. https://doi.org/10.1038/emboj.2010.37
  32. Singh, J., Verma, N.K., Kansagra, S.M., Kate, B.N., and Dey, C.S. (2007). Altered PPARgamma expression inhibits myogenic differentiation in C2C12 skeletal muscle cells. Mol. Cell. Biochem. 294, 163-171. https://doi.org/10.1007/s11010-006-9256-x
  33. Song, Y.J., and Lee, H. (2011). YB1/p32, a nuclear Y-box binding protein 1, is a novel regulator of myoblast differentiation that interacts with Msx1 homeoprotein. Exp. Cell Res. 316, 517-529.
  34. Spicer, D.B., Rhee, J., Cheung, W.L., and Lassar, A.B. (1996). Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein Twist. Science 272, 1476-1480. https://doi.org/10.1126/science.272.5267.1476
  35. Takada, I., Mihara, M., Suzawa, M., Ohtake, F., Kobayashi, S., Igarashi, M., Youn, M.Y., Takeyama, K., Nakamura, T., Mezaki, Y., et al. (2007). A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation. Nat. Cell Biol. 9, 1273-1285. https://doi.org/10.1038/ncb1647
  36. Takada, I., Kouzmenko, A.P., and Kato, S. (2009). Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis. Nat. Rev. Rheumatol. 5, 442-447. https://doi.org/10.1038/nrrheum.2009.137
  37. Tan, S.L., Nishi, M., Ohtsuka, T., Matsui, T., Takemoto, K., Kamio-Miura, A., Aburatani, H., Shinkai, Y., and Kageyama, R. (2012). Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development. Development 139, 3806-3816. https://doi.org/10.1242/dev.082198
  38. Tao, Y., Neppl, R.L., Huang, Z.P., Chen, J., Tang, R.H., Cao, R., Zhang, Y., Jin, S.W., and Wang, D.Z. (2011). The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly. J. Cell Biol. 194, 551-565. https://doi.org/10.1083/jcb.201010090
  39. Tapscott, S.J. (2005). The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription. Development 132, 2685-2695. https://doi.org/10.1242/dev.01874
  40. Tapscott, S.J. (2005). The circuitry of a master switch: Myod and the regulation of skeletal muscle gene transcription. Development 132, 2685-2695. https://doi.org/10.1242/dev.01874
  41. Thayer, M.J., Tapscott, S.J., Davis, R.L., Wright, W.E., Lassar, A.B., and Weintraub, H. (1989). Positive autoregulation of the myogenic determination gene MyoD1. Cell 58, 241-248. https://doi.org/10.1016/0092-8674(89)90838-6
  42. Tomczak, K.K., Marinescu, V.D., Ramoni, M.F., Sanoudou, D., Montanaro, F., Han, M., Kunkel, L.M., Kohane, I.S., and Beggs, A.H. (2004). Expression profiling and identification of novel genes involved in myogenic differentiation. FASEB J. 18, 403-405. https://doi.org/10.1096/fj.03-0568fje
  43. Wang, J., Helin, K., Jin, P., and Nadal-Ginard, B. (1995). Inhibition of in vitro myogenic differentiation by cellular transcription factor E2F1. Cell Growth Differ. 6, 1299-1306.
  44. Yang, L., Lawson, K.A., Teteak, C.J., Zou, J., Hacquebord, J., Patterson, D., Ghatan, A.C., Mei, Q., Zielinska-Kwiatkowska, A., Bain, S.D., et al. (2013). ESET histone methyltransferase is essential to hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates. Dev. Biol. 380, 99-110. https://doi.org/10.1016/j.ydbio.2013.04.031
  45. Yuan, P., Han, J., Guo, G., Orlov, Y.L., Huss, M., Loh, Y.H., Yaw, L.P., Robson, P., Lim, B., and Ng, H.H. (2009). Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev. 23, 2507-2520. https://doi.org/10.1101/gad.1831909
  46. Zhang, W., Behringer, R.R., and Olson, E.N. (1995). Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies. Genes Dev. 9, 1388-1399. https://doi.org/10.1101/gad.9.11.1388

Cited by

  1. Unexpected Distinct Roles of the Related Histone H3 Lysine 9 Methyltransferases G9a and G9a-Like Protein in Myoblasts vol.428, pp.11, 2016, https://doi.org/10.1016/j.jmb.2016.03.029
  2. SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy vol.49, pp.4, 2016, https://doi.org/10.5483/BMBRep.2016.49.4.031
  3. Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation vol.2, 2016, https://doi.org/10.1038/celldisc.2016.37
  4. A drive in SUVs: From development to disease vol.12, pp.3, 2017, https://doi.org/10.1080/15592294.2017.1281502
  5. Emerging role of SETDB1 as a therapeutic target vol.21, pp.3, 2017, https://doi.org/10.1080/14728222.2017.1279604
  6. The multifunctional RNA-binding protein hnRNPK is critical for the proliferation and differentiation of myoblasts vol.51, pp.7, 2018, https://doi.org/10.5483/BMBRep.2018.51.7.043
  7. Histone Methyltransferase SETDB1 Promotes the Progression of Colorectal Cancer by Inhibiting the Expression of TP53 vol.8, pp.16, 2017, https://doi.org/10.7150/jca.20482
  8. Memory enhancing effects of BPN14770, an allosteric inhibitor of phosphodiesterase-4D, in wild-type and humanized mice vol.43, pp.11, 2018, https://doi.org/10.1038/s41386-018-0178-6
  9. Novel Silicon Titanium Diboride Micropatterned Substrates for Cellular Patterning vol.244, pp.None, 2015, https://doi.org/10.1016/j.biomaterials.2020.119927
  10. Protonation states at different pH, conformational changes and impact of glycosylation in synapsin Ia vol.23, pp.31, 2021, https://doi.org/10.1039/d1cp00531f