Thanks to visit codestin.com
Credit goes to link.springer.com

Skip to main content
Springer Nature Link
Log in

Regulation of chromatin structure via histone post-translational modification and the link to carcinogenesis

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

The loss of genome integrity contributes to the development of tumors. Although genome instability is associated with virtually all tumor types including both solid and liquid tumors, the aberrant molecular origins that drive this instability are poorly understood. It is now becoming clear that epigenetics and specific histone post-translational modifications (PTMs) have essential roles in maintaining genome stability under normal conditions. A strong relationship exists between aberrant histone PTMs, genome instability, and tumorigenesis. Changes in the genomic location of specific histone PTMs or alterations in the steady-state levels of the PTM are the consequence of imbalances in the enzymes and their activities catalyzing the addition of PTMs (“writers”) or removal of PTMs (“erasers”). This review focuses on the misregulation of three specific types of histone PTMs: histone H3 phosphorylation at serines 10 and 28, H4 mono-methylation at lysine 20, and H2B ubiquitination at lysine 120. We discuss the normal regulation of these PTMs by the respective “writers” and “erasers” and the impact of their misregulation on genome stability.

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

Access this article

Log in via an institution

Subscribe and save

Springer+
from £29.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  1. Luger, K., et al. (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature, 389(6648), 251–260.

    PubMed  CAS  Google Scholar 

  2. Cohen, I., et al. (2011). Histone modifiers in cancer: friends or foes? Genes & Cancer, 2(6), 631–647.

    CAS  Google Scholar 

  3. Martin, C., & Zhang, Y. (2007). Mechanisms of epigenetic inheritance. Current Opinion in Cell Biology, 19(3), 266–272.

    PubMed  CAS  Google Scholar 

  4. Margueron, R., Trojer, P., & Reinberg, D. (2005). The key to development: interpreting the histone code? Current Opinion in Genetics & Development, 15(2), 163–176.

    CAS  Google Scholar 

  5. Horn, P. J., et al. (2002). Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes. Nature Structural Biology, 9(4), 263–267.

    PubMed  CAS  Google Scholar 

  6. Williamson, W. D., & Pinto, I. (2012). Histones and genome integrity. Frontiers in Bioscience: A Journal and Virtual Library, 17, 984–995.

    CAS  Google Scholar 

  7. Ruthenburg, A. J., Allis, C. D., & Wysocka, J. (2007). Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Molecular Cell, 25(1), 15–30.

    PubMed  CAS  Google Scholar 

  8. Kouzarides, T. (2007) SnapShot: histone-modifying enzymes. Cell, 131(4), 822.

    Google Scholar 

  9. Issa, J. P. (2004). CpG island methylator phenotype in cancer. Nature Reviews. Cancer, 4(12), 988–993.

    PubMed  CAS  Google Scholar 

  10. Kerzendorfer, C., & O’Driscoll, M. (2009). Human DNA damage response and repair deficiency syndromes: linking genomic instability and cell cycle checkpoint proficiency. DNA Repair, 8(9), 1139–1152.

    PubMed  CAS  Google Scholar 

  11. Geigl, J. B., et al. (2008). Defining ‘chromosomal instability’. Trends in Genetics: TIG, 24(2), 64–69.

    PubMed  CAS  Google Scholar 

  12. Schroeder, T. M. (1982). Genetically-determined chromosome instability syndromes. Cytogenetics and Cell Genetics, 33(1–2), 119–132.

    PubMed  CAS  Google Scholar 

  13. Huang, C. C., Banerjee, A., & Hou, Y. (1975). Chromosomal instability in cell lines derived from patients with xeroderma pigmentosum. Proceedings of the Society for Experimental Biology and Medicine, 148(4), 1244–1248.

    PubMed  CAS  Google Scholar 

  14. Chrzanowska, K. H., et al. (2012). Nijmegen breakage syndrome (NBS). Orphanet Journal of Rare Diseases, 7, 13.

    PubMed  Google Scholar 

  15. Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998). Genetic instabilities in human cancers. Nature, 396(6712), 643–649.

    PubMed  CAS  Google Scholar 

  16. Negrini, S., Gorgoulis, V. G., & Halazonetis, T. D. (2010). Genomic instability—an evolving hallmark of cancer. Nature Reviews. Molecular Cell Biology, 11(3), 220–228.

    PubMed  CAS  Google Scholar 

  17. Drobic, B., et al. (2010). Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex. Nucleic Acids Research, 38(10), 3196–3208.

    PubMed  CAS  Google Scholar 

  18. Prigent, C., & Dimitrov, S. (2003). Phosphorylation of serine 10 in histone H3, what for? Journal of Cell Science, 116(Pt 18), 3677–3685.

    PubMed  CAS  Google Scholar 

  19. Goto, H., et al. (2002). Aurora-B phosphorylates histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes to Cells: Devoted to Molecular & Cellular Mechanisms, 7(1), 11–17.

    CAS  Google Scholar 

  20. Mahadevan, L. C., Willis, A. C., & Barratt, M. J. (1991). Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell, 65(5), 775–783.

    PubMed  CAS  Google Scholar 

  21. Soloaga, A., et al. (2003). MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. The EMBO Journal, 22(11), 2788–2797.

    PubMed  CAS  Google Scholar 

  22. Lee, Y. J., & Shukla, S. D. (2007). Histone H3 phosphorylation at serine 10 and serine 28 is mediated by p38 MAPK in rat hepatocytes exposed to ethanol and acetaldehyde. European Journal of Pharmacology, 573(1–3), 29–38.

    PubMed  CAS  Google Scholar 

  23. Delcuve, G. P., Rastegar, M., & Davie, J. R. (2009). Epigenetic control. Journal of Cellular Physiology, 219(2), 243–250.

    PubMed  CAS  Google Scholar 

  24. Caivano, M., & Cohen, P. (2000). Role of mitogen-activated protein kinase cascades in mediating lipopolysaccharide-stimulated induction of cyclooxygenase-2 and IL-1 beta in RAW264 macrophages. Journal of Immunology, 164(6), 3018–3025.

    CAS  Google Scholar 

  25. Davie, J. R. (2003). MSK1 and MSK2 mediate mitogen- and stress-induced phosphorylation of histone H3: a controversy resolved. Science’s STKE: Signal Transduction Knowledge Environment, 2003(195), PE33.

    PubMed  Google Scholar 

  26. Strelkov, I. S., & Davie, J. R. (2002). Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts. Cancer Research, 62(1), 75–78.

    PubMed  CAS  Google Scholar 

  27. Macdonald, N., et al. (2005). Molecular basis for the recognition of phosphorylated and phosphoacetylated histone h3 by 14-3-3. Molecular Cell, 20(2), 199–211.

    PubMed  CAS  Google Scholar 

  28. Winter, S., Fischle, W., & Seiser, C. (2008). Modulation of 14-3-3 interaction with phosphorylated histone H3 by combinatorial modification patterns. Cell Cycle, 7(10), 1336–1342.

    PubMed  CAS  Google Scholar 

  29. Dunn, K. L., & Davie, J. R. (2005). Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28. Oncogene, 24(21), 3492–3502.

    PubMed  CAS  Google Scholar 

  30. Dyson, M. H., et al. (2005). MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28 via mitogen- and stress-activated kinase 1/2. Journal of Cell Science, 118(Pt 10), 2247–2259.

    PubMed  CAS  Google Scholar 

  31. Dunn, K. L., et al. (2009). Increased genomic instability and altered chromosomal protein phosphorylation timing in HRAS-transformed mouse fibroblasts. Genes, Chromosomes & Cancer, 48(5), 397–409.

    CAS  Google Scholar 

  32. Lim, J. H., et al. (2004). Chromosomal protein HMGN1 modulates histone H3 phosphorylation. Molecular Cell, 15(4), 573–584.

    PubMed  CAS  Google Scholar 

  33. Perez-Cadahia, B., Drobic, B., & Davie, J. R. (2009). H3 phosphorylation: dual role in mitosis and interphase. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire, 87(5), 695–709.

    PubMed  CAS  Google Scholar 

  34. Shaulian, E., & Karin, M. (2002). AP-1 as a regulator of cell life and death. Nature Cell Biology, 4(5), E131–E136.

    PubMed  CAS  Google Scholar 

  35. Jochum, W., Passegue, E., & Wagner, E. F. (2001). AP-1 in mouse development and tumorigenesis. Oncogene, 20(19), 2401–2412.

    PubMed  CAS  Google Scholar 

  36. Wagner, E. F. (2002). Functions of AP1 (Fos/Jun) in bone development. Annals of the Rheumatic Diseases, 61(Suppl 2), ii40–ii42.

    PubMed  CAS  Google Scholar 

  37. Grigoriadis, A. E., et al. (1993). Osteoblasts are target cells for transformation in c-fos transgenic mice. The Journal of Cell Biology, 122(3), 685–701.

    PubMed  CAS  Google Scholar 

  38. Ruther, U., Wagner, E. F., & Muller, R. (1985). Analysis of the differentiation-promoting potential of inducible c-fos genes introduced into embryonal carcinoma cells. The EMBO Journal, 4(7), 1775–1781.

    PubMed  CAS  Google Scholar 

  39. Wang, Z. Q., et al. (1995). c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun and the role of endogenous c-fos. Cancer Research, 55(24), 6244–6251.

    PubMed  CAS  Google Scholar 

  40. van den Berg, S., et al. (1993). Overexpression of c-fos increases recombination frequency in human osteosarcoma cells. Carcinogenesis, 14(5), 925–928.

    PubMed  Google Scholar 

  41. Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1997). Genetic instability in colorectal cancers. Nature, 386(6625), 623–627.

    PubMed  CAS  Google Scholar 

  42. Drobic, B., Espino, P. S., & Davie, J. R. (2004). Mitogen- and stress-activated protein kinase 1 activity and histone h3 phosphorylation in oncogene-transformed mouse fibroblasts. Cancer Research, 64(24), 9076–9079.

    PubMed  CAS  Google Scholar 

  43. Forbes, S. A., et al. (2011). COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Research, 39(Database issue), D945–D950.

    PubMed  CAS  Google Scholar 

  44. Forbes, S. A., et al. (2010). COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer. Nucleic Acids Research, 38(Database issue), D652–D657.

    PubMed  CAS  Google Scholar 

  45. Cerami, E., et al. (2012). The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discovery, 2(5), 401–404.

    PubMed  Google Scholar 

  46. Schiller, M., et al. (2006). Mitogen- and stress-activated protein kinase 1 is critical for interleukin-1-induced, CREB-mediated, c-fos gene expression in keratinocytes. Oncogene, 25(32), 4449–4457.

    PubMed  CAS  Google Scholar 

  47. Chang, S., et al. (2011). Mice lacking MSK1 and MSK2 show reduced skin tumor development in a two-stage chemical carcinogenesis model. Cancer Investigation, 29(3), 240–245.

    PubMed  CAS  Google Scholar 

  48. Kim, H. G., et al. (2008). Mitogen- and stress-activated kinase 1-mediated histone H3 phosphorylation is crucial for cell transformation. Cancer Research, 68(7), 2538–2547.

    PubMed  CAS  Google Scholar 

  49. Perez-Cadahia, B., et al. (2011). Role of MSK1 in the malignant phenotype of Ras-transformed mouse fibroblasts. The Journal of Biological Chemistry, 286(1), 42–49.

    PubMed  CAS  Google Scholar 

  50. Hendzel, M. J., et al. (1997). Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma, 106(6), 348–360.

    PubMed  CAS  Google Scholar 

  51. McManus, K. J., & Hendzel, M. J. (2006). The relationship between histone H3 phosphorylation and acetylation throughout the mammalian cell cycle. Biochemistry and Cell Biology = Biochimie et Biologie Cellulaire, 84(4), 640–657.

    PubMed  CAS  Google Scholar 

  52. Goto, H., et al. (1999). Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. The Journal of Biological Chemistry, 274(36), 25543–25549.

    PubMed  CAS  Google Scholar 

  53. Crosio, C., et al. (2002). Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Molecular and Cellular Biology, 22(3), 874–885.

    PubMed  CAS  Google Scholar 

  54. Kallio, M. J., et al. (2002). Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis. Current Biology: CB, 12(11), 900–905.

    PubMed  CAS  Google Scholar 

  55. Murata-Hori, M., Tatsuka, M., & Wang, Y. L. (2002). Probing the dynamics and functions of aurora B kinase in living cells during mitosis and cytokinesis. Molecular Biology of the Cell, 13(4), 1099–1108.

    PubMed  CAS  Google Scholar 

  56. Van Hooser, A., et al. (1998). Histone H3 phosphorylation is required for the initiation, but not maintenance, of mammalian chromosome condensation. Journal of Cell Science, 111(Pt 23), 3497–3506.

    PubMed  Google Scholar 

  57. Katayama, H., et al. (2004). Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nature Genetics, 36(1), 55–62.

    PubMed  CAS  Google Scholar 

  58. Ota, T., et al. (2002). Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Research, 62(18), 5168–5177.

    PubMed  CAS  Google Scholar 

  59. Tuncel, H., et al. (2012). Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer. Oncology Letters, 3(5), 1109–1114.

    PubMed  Google Scholar 

  60. Qi, G., et al. (2007). Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer. Virchows Archiv: An International Journal of Pathology, 450(3), 297–302.

    CAS  Google Scholar 

  61. Lee, E. C., et al. (2006). Targeting Aurora kinases for the treatment of prostate cancer. Cancer Research, 66(10), 4996–5002.

    PubMed  CAS  Google Scholar 

  62. Kurai, M., et al. (2005). Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma. Human Pathology, 36(12), 1281–1288.

    PubMed  CAS  Google Scholar 

  63. Sorrentino, R., et al. (2005). Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. The Journal of Clinical Endocrinology and Metabolism, 90(2), 928–935.

    PubMed  CAS  Google Scholar 

  64. Harrington, E. A., et al. (2004). VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nature Medicine, 10(3), 262–267.

    PubMed  CAS  Google Scholar 

  65. Hsu, J. Y., et al. (2000). Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell, 102(3), 279–291.

    PubMed  CAS  Google Scholar 

  66. de Carvalho, C. E., et al. (2008). LAB-1 antagonizes the Aurora B kinase in C. elegans. Genes & Development, 22(20), 2869–2885.

    Google Scholar 

  67. Ladha, J., et al. (2010). Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes. Cancer Research, 70(16), 6437–6447.

    PubMed  CAS  Google Scholar 

  68. Rea, S., et al. (2000). Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature, 406(6796), 593–599.

    PubMed  CAS  Google Scholar 

  69. Lachner, M., O’Sullivan, R. J., & Jenuwein, T. (2003). An epigenetic road map for histone lysine methylation. Journal of Cell Science, 116(Pt 11), 2117–2124.

    PubMed  CAS  Google Scholar 

  70. He, Y., et al. (2012). Targeting protein lysine methylation and demethylation in cancers. Acta biochimica et biophysica Sinica, 44(1), 70–79.

    PubMed  Google Scholar 

  71. Steward, M. M., et al. (2006). Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes. Nature Structural & Molecular Biology, 13(9), 852–854.

    CAS  Google Scholar 

  72. Santos-Rosa, H., et al. (2002). Active genes are tri-methylated at K4 of histone H3. Nature, 419(6905), 407–411.

    PubMed  CAS  Google Scholar 

  73. Wang, H., et al. (2001). Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Molecular Cell, 8(6), 1207–1217.

    PubMed  CAS  Google Scholar 

  74. Beck, D. B., et al. (2012). PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription. Genes & Development, 26(4), 325–337.

    CAS  Google Scholar 

  75. Rice, J. C., et al. (2002). Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes. Genes & Development, 16(17), 2225–2230.

    CAS  Google Scholar 

  76. Nishioka, K., et al. (2002). PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Molecular Cell, 9(6), 1201–1213.

    PubMed  CAS  Google Scholar 

  77. Xiao, B., et al. (2005). Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes & Development, 19(12), 1444–1454.

    CAS  Google Scholar 

  78. Couture, J. F., et al. (2005). Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Genes & Development, 19(12), 1455–1465.

    CAS  Google Scholar 

  79. Houston, S. I., et al. (2008). Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability. The Journal of Biological Chemistry, 283(28), 19478–19488.

    PubMed  CAS  Google Scholar 

  80. Sims, J. K., et al. (2006). A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. The Journal of Biological Chemistry, 281(18), 12760–12766.

    PubMed  CAS  Google Scholar 

  81. Biron, V. L., et al. (2004). Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. Developmental Biology, 276(2), 337–351.

    PubMed  CAS  Google Scholar 

  82. Lu, X., et al. (2008). The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure. Nature Structural & Molecular Biology, 15(10), 1122–1124.

    CAS  Google Scholar 

  83. Davey, C. A., et al. (2002). Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. Journal of Molecular Biology, 319(5), 1097–1113.

    PubMed  CAS  Google Scholar 

  84. Dorigo, B., et al. (2003). Chromatin fiber folding: requirement for the histone H4 N-terminal tail. Journal of Molecular Biology, 327(1), 85–96.

    PubMed  CAS  Google Scholar 

  85. Liu, W., et al. (2010). PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature, 466(7305), 508–512.

    PubMed  CAS  Google Scholar 

  86. Oda, H., et al. (2009). Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development. Molecular and Cellular Biology, 29(8), 2278–2295.

    PubMed  CAS  Google Scholar 

  87. Yang, F., et al. (2012). SET8 promotes epithelial–mesenchymal transition and confers TWIST dual transcriptional activities. The EMBO Journal, 31(1), 110–123.

    PubMed  CAS  Google Scholar 

  88. Kalakonda, N., et al. (2008). Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene, 27(31), 4293–4304.

    PubMed  CAS  Google Scholar 

  89. Barski, A., et al. (2007). High-resolution profiling of histone methylations in the human genome. Cell, 129(4), 823–837.

    PubMed  CAS  Google Scholar 

  90. Talasz, H., et al. (2005). Histone H4-lysine 20 monomethylation is increased in promoter and coding regions of active genes and correlates with hyperacetylation. The Journal of Biological Chemistry, 280(46), 38814–38822.

    PubMed  CAS  Google Scholar 

  91. Vakoc, C. R., et al. (2006). Profile of histone lysine methylation across transcribed mammalian chromatin. Molecular and Cellular Biology, 26(24), 9185–9195.

    PubMed  CAS  Google Scholar 

  92. Loenarz, C., & Schofield, C. J. (2008). Expanding chemical biology of 2-oxoglutarate oxygenases. Nature Chemical Biology, 4(3), 152–156.

    PubMed  CAS  Google Scholar 

  93. Bjorkman, M., et al. (2012). Systematic knockdown of epigenetic enzymes identifies a novel histone demethylase PHF8 overexpressed in prostate cancer with an impact on cell proliferation, migration and invasion. Oncogene, 31(29), 3444–3456.

    PubMed  CAS  Google Scholar 

  94. Rose, N. R., et al. (2010). Selective inhibitors of the JMJD2 histone demethylases: combined nondenaturing mass spectrometric screening and crystallographic approaches. Journal of Medicinal Chemistry, 53(4), 1810–1818.

    PubMed  CAS  Google Scholar 

  95. King, O. N., et al. (2010). Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors. PloS One, 5(11), e15535.

    PubMed  Google Scholar 

  96. Chen, H. Y., et al. (1998). Ubiquitination of histone H3 in elongating spermatids of rat testes. The Journal of Biological Chemistry, 273(21), 13165–13169.

    PubMed  CAS  Google Scholar 

  97. Thorne, A. W., et al. (1987). The structure of ubiquitinated histone H2B. The EMBO Journal, 6(4), 1005–1010.

    PubMed  CAS  Google Scholar 

  98. Osley, M. A. (2006). Regulation of histone H2A and H2B ubiquitylation. Briefings in Functional Genomics & Proteomics, 5(3), 179–189.

    CAS  Google Scholar 

  99. Wang, H., et al. (2004). Role of histone H2A ubiquitination in Polycomb silencing. Nature, 431(7010), 873–878.

    PubMed  CAS  Google Scholar 

  100. Pickart, C. M. (2001). Mechanisms underlying ubiquitination. Annual Review of Biochemistry, 70, 503–533.

    PubMed  CAS  Google Scholar 

  101. Fierz, B., et al. (2011). Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction. Nature Chemical Biology, 7(2), 113–119.

    PubMed  CAS  Google Scholar 

  102. Johnsen, S. A. (2012). The enigmatic role of H2Bub1 in cancer. FEBS Letters, 586(11), 1592–1601.

    PubMed  CAS  Google Scholar 

  103. Kim, J., et al. (2009). RAD6-mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell, 137(3), 459–471.

    PubMed  CAS  Google Scholar 

  104. Shema, E., et al. (2008). The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes & Development, 22(19), 2664–2676.

    CAS  Google Scholar 

  105. Chernikova, S. B., et al. (2010). Deficiency in Bre1 impairs homologous recombination repair and cell cycle checkpoint response to radiation damage in mammalian cells. Radiation Research, 174(5), 558–565.

    PubMed  CAS  Google Scholar 

  106. Hahn, M. A., et al. (2012). The tumor suppressor CDC73 interacts with the ring finger proteins RNF20 and RNF40 and is required for the maintenance of histone 2B monoubiquitination. Human Molecular Genetics, 21(3), 559–568.

    PubMed  CAS  Google Scholar 

  107. Prenzel, T., et al. (2011). Estrogen-dependent gene transcription in human breast cancer cells relies upon proteasome-dependent monoubiquitination of histone H2B. Cancer Research, 71(17), 5739–5753.

    PubMed  CAS  Google Scholar 

  108. Zhao, Y., et al. (2008). A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Molecular Cell, 29(1), 92–101.

    PubMed  CAS  Google Scholar 

  109. Zhang, X. Y., et al. (2008). The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Molecular Cell, 29(1), 102–111.

    PubMed  Google Scholar 

  110. Zhang, Y., et al. (2011). Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer. Journal of Cancer Research and Clinical Oncology, 137(8), 1245–1253.

    PubMed  CAS  Google Scholar 

  111. Liu, Y. L., et al. (2010). Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer. Journal of Gastroenterology and Hepatology, 25(11), 1800–1805.

    PubMed  Google Scholar 

  112. Davie, J. R., & Murphy, L. C. (1994). Inhibition of transcription selectively reduces the level of ubiquitinated histone H2B in chromatin. Biochemical and Biophysical Research Communications, 203(1), 344–350.

    PubMed  CAS  Google Scholar 

  113. Davie, J. R., & Murphy, L. C. (1990). Level of ubiquitinated histone H2B in chromatin is coupled to ongoing transcription. Biochemistry, 29(20), 4752–4757.

    PubMed  CAS  Google Scholar 

  114. Li, B., Carey, M., & Workman, J. L. (2007). The role of chromatin during transcription. Cell, 128(4), 707–719.

    PubMed  CAS  Google Scholar 

  115. Belotserkovskaya, R., et al. (2003). FACT facilitates transcription-dependent nucleosome alteration. Science, 301(5636), 1090–1093.

    PubMed  CAS  Google Scholar 

  116. Pavri, R., et al. (2006). Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell, 125(4), 703–717.

    PubMed  CAS  Google Scholar 

  117. Fuchs, G., et al. (2012). RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation. Molecular Cell, 46(5), 662–673.

    PubMed  CAS  Google Scholar 

  118. Zhang, F., & Yu, X. (2011). WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription. Molecular Cell, 41(4), 384–397.

    PubMed  CAS  Google Scholar 

  119. Shema, E., et al. (2011). RNF20 inhibits TFIIS-facilitated transcriptional elongation to suppress pro-oncogenic gene expression. Molecular Cell, 42(4), 477–488.

    PubMed  CAS  Google Scholar 

  120. Karpiuk, O., et al. (2012). The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. Molecular Cell, 46(5), 705–713.

    PubMed  CAS  Google Scholar 

  121. Shiloh, Y., et al. (2011). RNF20-RNF40: a ubiquitin-driven link between gene expression and the DNA damage response. FEBS Letters, 585(18), 2795–2802.

    PubMed  CAS  Google Scholar 

  122. Nakamura, K., et al. (2011). Regulation of homologous recombination by RNF20-dependent H2B ubiquitination. Molecular Cell, 41(5), 515–528.

    PubMed  CAS  Google Scholar 

  123. Moyal, L., et al. (2011). Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Molecular Cell, 41(5), 529–542.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Geneviève Delcuve for preparation of the manuscript. Research support by establishment and operating grants from the Manitoba Health Research Council (MHRC) (KJM), CancerCare Manitoba (KJM), the Canadian Institutes of Health Research to KJM (MOP 115179) and JRD (MOP 9186), the Canadian Cancer Society Research Institute (JRD 017136), a CIHR/MHRC New Investigator Award (KJM), a Canada Research Chair to JRD, a Terry Fox Graduate Studentship (LLT), an MHRC/CancerCare Manitoba Studentship (BJG), and a University of Manitoba Undergraduate Summer Studentship (LS) are gratefully acknowledged. We acknowledge the strong support of the Manitoba Institute of Child Health and the Manitoba Institute of Cell Biology.

Author information

Authors and Affiliations

  1. Department of Biochemistry & Medical Genetics, University of Manitoba, Winnipeg, MB, Canada

    Laura L. Thompson, Brent J. Guppy, Laryssa Sawchuk, James R. Davie & Kirk J. McManus

  2. Manitoba Institute of Cell Biology, CancerCare Manitoba, ON6010-675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada

    Laura L. Thompson, Brent J. Guppy, Laryssa Sawchuk, James R. Davie & Kirk J. McManus

  3. Manitoba Institute of Child Health, John Buhler Research Centre, 715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada

    James R. Davie

Authors
  1. Laura L. Thompson
    View author publications

    Search author on:PubMed Google Scholar

  2. Brent J. Guppy
    View author publications

    Search author on:PubMed Google Scholar

  3. Laryssa Sawchuk
    View author publications

    Search author on:PubMed Google Scholar

  4. James R. Davie
    View author publications

    Search author on:PubMed Google Scholar

  5. Kirk J. McManus
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to James R. Davie or Kirk J. McManus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thompson, L.L., Guppy, B.J., Sawchuk, L. et al. Regulation of chromatin structure via histone post-translational modification and the link to carcinogenesis. Cancer Metastasis Rev 32, 363–376 (2013). https://doi.org/10.1007/s10555-013-9434-8

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1007/s10555-013-9434-8

Keywords