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Histone onco-modifications

Oncogene volume 30, pages 3391–3403 (2011)Cite this article

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Abstract

Post-translational modification of histones provides an important regulatory platform for processes such as gene expression, DNA replication and repair, chromosome condensation and segregation and apoptosis. Disruption of these processes has been linked to the multistep process of carcinogenesis. We review the aberrant covalent histone modifications observed in cancer, and discuss how these epigenetic changes, caused by alterations in histone-modifying enzymes, can contribute to the development of a variety of human cancers. As a conclusion, a new terminology ‘histone onco-modifications’ is proposed to describe post-translational modifications of histones, which have been linked to cancer. This new term would take into account the active contribution and importance of these histone modifications in the development and progression of cancer.

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Abbreviations

53BP1:

tumor protein p53 binding protein 1

ac:

acetylated

ASF1A:

anti-silencing function 1 homolog A

BRCA1:

breast cancer 1, early onset

CDK8:

cyclin dependent kinase 8

ChIP:

chromatin immunoprecipitation

CpG:

cytosine-phosphate-guanine

DBC1:

deleted in breast cancer 1

DNMT:

DNA methyltransferase

EZH2:

Enhancer of zeste homolog 2

GASC1:

gene amplified in squamous cell carcinoma 1

H2A:

histone 2A

H2B:

histone 2B

H3:

histone 3

H4:

histone 4

HAT:

histone acetyltransferase

HDAC:

histone deacetylase

HDACI:

HDAC inhibitor

HDM:

histone demethylase

HIRA:

histone cell cycle regulation-defective homolog A

hMOF:

human orthologue of the Drosophila melanogaster males absent on the first gene

HMT:

histone methyltransferase

JARID1:

jumonji AT-rich interactive domain 1

JMJD3:

jumonji domain containing 3

K:

lysine

me:

methylated

LSD1:

lysine-specific histone demethylase 1

Mdc1:

mediator of DNA-damage checkpoint 1

mH2A:

macro histone 2A

MLL:

mixed lineage leukaemia

S:

serine

SIRT1:

sirtuin 1

SMYD3:

SET and MYND domain-containing protein 3

T:

threonine

ub:

ubiquitinylated

UTX:

ubiquitously transcribed tetratricopeptide repeat, X chromosome

Vegfr1:

vascular endothelial growth factor receptor 1

References

  • Agger K, Cloos PA, Rudkjaer L, Williams K, Andersen G, Christensen J et al. (2009). The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev 23: 1171–1176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ajiro K, Scoltock AB, Smith LK, Ashasima M, Cidlowski JA . (2010). Reciprocal epigenetic modification of histone H2B occurs in chromatin during apoptosis in vitro and in vivo. Cell Death Differ 17: 984–993.

    CAS  PubMed  Google Scholar 

  • Allis CD, Berger SL, Cote J, Dent S, Jenuwien T, Kouzarides T et al. (2007). New nomenclature for chromatin-modifying enzymes. Cell 131: 633–636.

    CAS  PubMed  Google Scholar 

  • Amente S, Bertoni A, Morano A, Lania L, Avvedimento EV, Majello B . (2010). LSD1-mediated demethylation of histone H3 lysine 4 triggers Myc-induced transcription. Oncogene 29: 3691–3702.

    CAS  PubMed  Google Scholar 

  • Anderton JA, Bose S, Vockerodt M, Vrzalikova K, Wei W, Kuo M et al. (2011). The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's lymphoma. Oncogene 2011: 17.

    Google Scholar 

  • Ashktorab H, Belgrave K, Hosseinkhah F, Brim H, Nouraie M, Takkikto M et al. (2009). Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Dig Dis Sci 54: 2109–2117.

    CAS  PubMed  Google Scholar 

  • Bachman KE, Park BH, Rhee I, Rajagopalan H, Herman JG, Baylin SB et al. (2003). Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene (2010). Cancer Cell 3: 89–95.

    CAS  PubMed  Google Scholar 

  • Bagnyukova TV, Tryndyak VP, Montgomery B, Churchwell MI, Karpf AR, James SR et al. (2008). Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene. Carcinogenesis 29: 638–646.

    CAS  PubMed  Google Scholar 

  • Bai X, Wu L, Liang T, Liu Z, Li J, Li D et al. (2008). Overexpression of myocyte enhancer factor 2 and histone hyperacetylation in hepatocellular carcinoma. J Cancer Res Clin Oncol 134: 83–91.

    CAS  PubMed  Google Scholar 

  • Barlesi F, Giaccone G, Gallegos-Ruiz MI, Loundou A, Span SW, Lefesvre P et al. (2007). Global histone modifications predict prognosis of resected non small-cell lung cancer. J Clin Oncol 25: 4358–4364.

    PubMed  Google Scholar 

  • Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z et al. (2007). High-resolution profiling of histone methylations in the human genome. Cell 129: 823–837.

    CAS  PubMed  Google Scholar 

  • Baylin SB, Ohm JE . (2006). Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6: 107–116.

    CAS  PubMed  Google Scholar 

  • Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A . (2009). An operational definition of epigenetics. Genes Dev 23: 781–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J et al. (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315–326.

    CAS  PubMed  Google Scholar 

  • Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C et al. (2007). The polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev 21: 525–530.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cedar H, Bergman Y . (2009). Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10: 295–304.

    CAS  PubMed  Google Scholar 

  • Cha EJ, Noh SJ, Kwon KS, Kim CY, Park BH, Park HS et al. (2009). Expression of DBC1 and SIRT1 is associated with poor prognosis of gastric carcinoma. Clin Cancer Res 15: 4453–4459.

    CAS  PubMed  Google Scholar 

  • Chen MW, Hua KT, Kao HJ, Chi CC, Wei LH, Johansson G et al. (2010). H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM. Cancer Res 70: 7830–7840.

    CAS  PubMed  Google Scholar 

  • Chen WY, Wang DH, Yen RC, Luo J, Gu W, Baylin SB . (2005). Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell 123: 437–448.

    CAS  PubMed  Google Scholar 

  • Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T et al. (2006). The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 442: 307–311.

    CAS  PubMed  Google Scholar 

  • Cosgrove MS, Boeke JD, Wolberger C . (2004). Regulated nucleosome mobility and the histone code. Nat Struct Mol Biol 11: 1037–1043.

    CAS  PubMed  Google Scholar 

  • Das C, Lucia MS, Hansen KC, Tyler JK . (2009). CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459: 113–117.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dou Y, Milne TA, Tackett AJ, Smith ER, Fukuda A, Wysocka J et al. (2005). Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 121: 873–885.

    CAS  PubMed  Google Scholar 

  • Dutta D, Ray S, Home P, Saha B, Wang S, Sheibani N et al. (2010). Regulation of angiogenesis by histone chaperone HIRA-mediated Incorporation of lysine 56-acetylated histone H3.3 at chromatin domains of endothelial genes. J Biol Chem 285: 41567–41577.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ebbs ML, Bartee L, Bender J . (2005). H3 lysine 9 methylation is maintained on a transcribed inverted repeat by combined action of SUVH6 and SUVH4 methyltransferases. Mol Cell Biol 25: 10507–10515.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ellinger J, Kahl P, Mertens C, Rogenhofer S, Hauser S, Hartmann W et al. (2010). Prognostic relevance of global histone H3 lysine 4 (H3K4) methylation in renal cell carcinoma. Int J Cancer 127: 2360–2366.

    CAS  PubMed  Google Scholar 

  • Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM et al. (2009). Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res 69: 3802–3809.

    CAS  PubMed  Google Scholar 

  • Feinberg AP, Vogelstein B . (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301: 89–92.

    CAS  PubMed  Google Scholar 

  • Ferrari R, Pellegrini M, Horwitz GA, Xie W, Berk AJ, Kurdistani SK . (2008). Epigenetic reprogramming by adenovirus e1a. Science 321: 1086–1088.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fischle W, Wang Y, Allis CD . (2003). Binary switches and modification cassettes in histone biology and beyond. Nature 425: 475–479.

    CAS  PubMed  Google Scholar 

  • Fournier C, Goto Y, Ballestar E, Delaval K, Hever AM, Esteller M et al. (2002). Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. EMBO J 21: 6560–6570.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G et al. (2005). Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37: 391–400.

    CAS  PubMed  Google Scholar 

  • Francis NJ, Kingston RE, Woodcock CL . (2004). Chromatin compaction by a polycomb group protein complex. Science 306: 1574–1577.

    CAS  PubMed  Google Scholar 

  • Fuks F . (2005). DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev 15: 490–495.

    CAS  PubMed  Google Scholar 

  • Fullgrabe J, Hajji N, Joseph B . (2010). Cracking the death code: apoptosis-related histone modifications. Cell Death Differ 17: 1238–1243.

    CAS  PubMed  Google Scholar 

  • Gonzalo S, Garcia-Cao M, Fraga MF, Schotta G, Peters AH, Cotter SE et al. (2005). Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol 7: 420–428.

    CAS  PubMed  Google Scholar 

  • Guo J, Cai J, Yu L, Tang H, Chen C, Wang Z . (2011). EZH2 regulates expression of p57 and contributes to progression of ovarian cancer in vitro and in vivo. Cancer Sci 102: 530–539.

    CAS  PubMed  Google Scholar 

  • Hajji N, Wallenborg K, Vlachos P, Nyman U, Hermanson O, Joseph B . (2008). Combinatorial action of the HDAC inhibitor trichostatin A and etoposide induces caspase-mediated AIF-dependent apoptotic cell death in non-small cell lung carcinoma cells. Oncogene 27: 3134–3144.

    CAS  PubMed  Google Scholar 

  • Hajji N, Wallenborg K, Vlachos P, Fullgrabe J, Hermanson O, Joseph B . (2010). Opposing effects of hMOF and SIRT1 on H4K16 acetylation and the sensitivity to the topoisomerase II inhibitor etoposide. Oncogene 29: 2192–2204.

    CAS  PubMed  Google Scholar 

  • Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M et al. (2004). SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 6: 731–740.

    CAS  PubMed  Google Scholar 

  • Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y et al. (2006). Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci 97: 113–118.

    CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA . (2000). The hallmarks of cancer. Cell 100: 57–70.

    CAS  PubMed  Google Scholar 

  • Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS, Monrad A et al. (2008). A model for transmission of the H3K27me3 epigenetic mark. Nat Cell Biol 10: 1291–1300.

    CAS  PubMed  Google Scholar 

  • Hayami S, Kelly JD, Cho HS, Yoshimatsu M, Unoki M, Tsunoda T et al. (2011). Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer 128: 574–586.

    CAS  PubMed  Google Scholar 

  • He LR, Liu MZ, Li BK, Rao HL, Liao YJ, Guan XY et al. (2009). Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma. BMC Cancer 9: 461.

    PubMed  PubMed Central  Google Scholar 

  • Henckel A, Nakabayashi K, Sanz LA, Feil R, Hata K, Arnaud P . (2009). Histone methylation is mechanistically linked to DNA methylation at imprinting control regions in mammals. Hum Mol Genet 18: 3375–3383.

    CAS  PubMed  Google Scholar 

  • Hida Y, Kubo Y, Murao K, Arase S . (2007). Strong expression of a longevity-related protein, SIRT1, in Bowen's disease. Arch Dermatol Res 299: 103–106.

    CAS  PubMed  Google Scholar 

  • Horwitz GA, Zhang K, McBrian MA, Grunstein M, Kurdistani SK, Berk AJ . (2008). Adenovirus small e1a alters global patterns of histone modification. Science 321: 1084–1085.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J, Dorsey J, Chuikov S, Perez-Burgos L, Zhang X, Jenuwein T et al. (2010). G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem 285: 9636–9641.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huffman DM, Grizzle WE, Bamman MM, Kim JS, Eltoum IA, Elgavish A et al. (2007). SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res 67: 6612–6618.

    CAS  PubMed  Google Scholar 

  • Jang KY, Hwang SH, Kwon KS, Kim KR, Choi HN, Lee NR et al. (2008). SIRT1 expression is associated with poor prognosis of diffuse large B-cell lymphoma. Am J Surg Pathol 32: 1523–1531.

    PubMed  Google Scholar 

  • Jenuwein T, Allis CD . (2001). Translating the histone code. Science 293: 1074–1080.

    CAS  PubMed  Google Scholar 

  • Jorgensen S, Elvers I, Trelle MB, Menzel T, Eskildsen M, Jensen ON et al. (2007). The histone methyltransferase SET8 is required for S-phase progression. J Cell Biol 179: 1337–1345.

    PubMed  PubMed Central  Google Scholar 

  • Kapoor A, Goldberg MS, Cumberland LK, Ratnakumar K, Segura MF, Emanuel PO et al. (2010). The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature 468: 1105–1109.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kapoor-Vazirani P, Kagey JD, Powell DR, Vertino PM . (2008). Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity. Cancer Res 68: 6810–6821.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Khare SP, Sharma A, Deodhar KK, Gupta S . (2011). Overexpression of histone variant H2A 1 and cellular transformation are related in N-nitrosodiethylamine-induced sequential hepatocarcinogenesis. Exp Biol Med (Maywood) 236: 30–35.

    CAS  Google Scholar 

  • Khorasanizadeh S . (2004). The nucleosome: from genomic organization to genomic regulation. Cell 116: 259–272.

    CAS  PubMed  Google Scholar 

  • Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA et al. (2003). EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA 100: 11606–11611.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klose RJ, Zhang Y . (2007). Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8: 307–318.

    CAS  PubMed  Google Scholar 

  • Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR et al. (2008). Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS One 3: e2037.

    PubMed  PubMed Central  Google Scholar 

  • Kondo Y, Shen L, Suzuki S, Kurokawa T, Masuko K, Tanaka Y et al. (2007). Alterations of DNA methylation and histone modifications contribute to gene silencing in hepatocellular carcinomas. Hepatol Res 37: 974–983.

    CAS  PubMed  Google Scholar 

  • Kornberg RD, Lorch Y . (1999). Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98: 285–294.

    CAS  PubMed  Google Scholar 

  • Kourmouli N, Jeppesen P, Mahadevhaiah S, Burgoyne P, Wu R, Gilbert DM et al. (2004). Heterochromatin and tri-methylated lysine 20 of histone H4 in animals. J Cell Sci 117: 2491–2501.

    CAS  PubMed  Google Scholar 

  • Kouzarides T . (2007). Chromatin modifications and their function. Cell 128: 693–705.

    CAS  PubMed  Google Scholar 

  • Kovalchuk O, Tryndyak VP, Montgomery B, Boyko A, Kutanzi K, Zemp F et al. (2007). Estrogen-induced rat breast carcinogenesis is characterized by alterations in DNA methylation, histone modifications and aberrant microRNA expression. Cell Cycle 6: 2010–2018.

    CAS  PubMed  Google Scholar 

  • Krivtsov AV, Armstrong SA . (2007). MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 7: 823–833.

    CAS  PubMed  Google Scholar 

  • Kurdistani SK . (2011). Histone modifications in cancer biology and prognosis. Prog Drug Res 67: 91–106.

    CAS  PubMed  Google Scholar 

  • Kwon MJ, Kim SS, Choi YL, Jung HS, Balch C, Kim SH et al. (2010). Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifications. Carcinogenesis 31: 974–983.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee H, Kim KR, Noh SJ, Park HS, Kwon KS, Park BH et al. (2011). Expression of DBC1 and SIRT1 is associated with poor prognosis for breast carcinoma. Hum Pathol 42: 204–213.

    CAS  PubMed  Google Scholar 

  • Li X, Corsa CA, Pan PW, Wu L, Ferguson D, Yu X et al. (2010). MOF and H4 K16 acetylation play important roles in DNA damage repair by modulating recruitment of DNA damage repair protein Mdc1. Mol Cell Biol 30: 5335–5347.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu BL, Cheng JX, Zhang X, Wang R, Zhang W, Lin H et al. (2010a). Global histone modification patterns as prognostic markers to classify glioma patients. Cancer Epidemiol Biomarkers Prev 19: 2888–2896.

    CAS  PubMed  Google Scholar 

  • Liu G, Bollig-Fischer A, Kreike B, van de Vijver MJ, Abrams J, Ethier SP et al. (2009). Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer. Oncogene 28: 4491–4500.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Takeda S, Kumar R, Westergard TD, Brown EJ, Pandita TK et al. (2010b). Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint. Nature 467: 343–346.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lu C, Han HD, Mangala LS, Ali-Fehmi R, Newton CS, Ozbun L et al. (2010). Regulation of tumor angiogenesis by EZH2. Cancer Cell 18: 185–197.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lu PJ, Sundquist K, Baeckstrom D, Poulsom R, Hanby A, Meier-Ewert S et al. (1999). A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer. J Biol Chem 274: 15633–15645.

    CAS  PubMed  Google Scholar 

  • Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ . (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389: 251–260.

    CAS  PubMed  Google Scholar 

  • Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R . (2007). FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12: 1247–1252.

    CAS  PubMed  Google Scholar 

  • Manuyakorn A, Paulus R, Farrell J, Dawson NA, Tze S, Cheung-Lau G et al. (2010). Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J Clin Oncol 28: 1358–1365.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez-Garcia E, Licht JD . (2010). Deregulation of H3K27 methylation in cancer. Nat Genet 42: 100–101.

    CAS  PubMed  Google Scholar 

  • Masumoto H, Hawke D, Kobayashi R, Verreault A . (2005). A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature 436: 294–298.

    CAS  PubMed  Google Scholar 

  • Maze I, Covington III HE, Dietz DM, LaPlant Q, Renthal W, Russo SJ et al. (2010). Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science 327: 213–216.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Michaud-Levesque J, Richard S . (2009). Thrombospondin-1 is a transcriptional repression target of PRMT6. J Biol Chem 284: 21338–21346.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G et al. (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448: 553–560.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S et al. (2010). Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 17: 1144–1151.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mohamed MA, Greif PA, Diamond J, Sharaf O, Maxwell P, Montironi R et al. (2007). Epigenetic events, remodelling enzymes and their relationship to chromatin organization in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. BJU Int 99: 908–915.

    CAS  PubMed  Google Scholar 

  • Muller-Tidow C, Klein HU, Hascher A, Isken F, Tickenbrock L, Thoennissen N et al. (2010). Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia. Blood 116: 3564–3571.

    PubMed  PubMed Central  Google Scholar 

  • Neal KC, Pannuti A, Smith ER, Lucchesi JC . (2000). A new human member of the MYST family of histone acetyl transferases with high sequence similarity to Drosophila MOF. Biochim Biophys Acta 1490: 170–174.

    CAS  PubMed  Google Scholar 

  • Nguyen CT, Weisenberger DJ, Velicescu M, Gonzales FA, Lin JC, Liang G et al. (2002). Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2’-deoxycytidine. Cancer Res 62: 6456–6461.

    CAS  PubMed  Google Scholar 

  • Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y et al. (2002). PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell 9: 1201–1213.

    CAS  PubMed  Google Scholar 

  • Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z et al. (2007). DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448: 714–717.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Orzan F, Pellegatta S, Poliani L, Pisati F, Caldera V, Menghi F et al. (2010). Enhancer of zeste 2 (Ezh2) is up-regulated in malignant gliomas and in glioma stem-like cells. Neuropathol Appl Neurobiol 2010: 1365–2990.

    Google Scholar 

  • Ozdag H, Teschendorff AE, Ahmed AA, Hyland SJ, Blenkiron C, Bobrow L et al. (2006). Differential expression of selected histone modifier genes in human solid cancers. BMC Genomics 7: 90.

    PubMed  PubMed Central  Google Scholar 

  • Park YS, Jin MY, Kim YJ, Yook JH, Kim BS, Jang SJ . (2008). The global histone modification pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma. Ann Surg Oncol 15: 1968–1976.

    PubMed  Google Scholar 

  • Pauler FM, Sloane MA, Huang R, Regha K, Koerner MV, Tamir I et al. (2009). H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome. Genome Res 19: 221–233.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pfister S, Rea S, Taipale M, Mendrzyk F, Straub B, Ittrich C et al. (2008). The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma. Int J Cancer 122: 1207–1213.

    CAS  PubMed  Google Scholar 

  • Pogribny IP, Ross SA, Tryndyak VP, Pogribna M, Poirier LA, Karpinets TV . (2006). Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats. Carcinogenesis 27: 1180–1186.

    CAS  PubMed  Google Scholar 

  • Pogribny IP, Tryndyak VP, Muskhelishvili L, Rusyn I, Ross SA . (2007). Methyl deficiency, alterations in global histone modifications, and carcinogenesis. J Nutr 137: 216S–222S.

    CAS  PubMed  Google Scholar 

  • Rajendran G, Shanmuganandam K, Bendre A, Mujumdar D, Goel A, Shiras A . (2011). Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas. J Neurooncol 2011: 13.

    Google Scholar 

  • Rao ZY, Cai MY, Yang GF, He LR, Mai SJ, Hua WF et al. (2010). EZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-beta1 and is a predictor of outcome in ovarian carcinoma patients. Carcinogenesis 31: 1576–1583.

    CAS  PubMed  Google Scholar 

  • Ren TN, Wang JS, He YM, Xu CL, Wang SZ, Xi T . (2010). Effects of SMYD3 over-expression on cell cycle acceleration and cell proliferation in MDA-MB-231 human breast cancer cells. Med Oncol (e-pub ahead of print).

  • Ringrose L, Ehret H, Paro R . (2004). Distinct contributions of histone H3 lysine 9 and 27 methylation to locus-specific stability of polycomb complexes. Mol Cell 16: 641–653.

    CAS  PubMed  Google Scholar 

  • Robertson KD . (2005). DNA methylation and human disease. Nat Rev Genet 6: 597–610.

    CAS  PubMed  Google Scholar 

  • Rufiange A, Jacques PE, Bhat W, Robert F, Nourani A . (2007). Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1. Mol Cell 27: 393–405.

    CAS  PubMed  Google Scholar 

  • Rundlett SE, Carmen AA, Suka N, Turner BM, Grunstein M . (1998). Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3. Nature 392: 831–835.

    CAS  PubMed  Google Scholar 

  • Ruthenburg AJ, Allis CD, Wysocka J . (2007). Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell 25: 15–30.

    CAS  PubMed  Google Scholar 

  • Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G et al. (2004). A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev 18: 1251–1262.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R et al. (2009). Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res 69: 2065–2071.

    CAS  PubMed  Google Scholar 

  • Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S et al. (2009). Global levels of histone modifications predict prognosis in different cancers. Am J Pathol 174: 1619–1628.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M et al. (2005). Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435: 1262–1266.

    CAS  PubMed  Google Scholar 

  • Sharma S, Kelly TK, Jones PA . (2010). Epigenetics in cancer. Carcinogenesis 31: 27–36.

    CAS  PubMed  Google Scholar 

  • Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X et al. (2008). EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell 32: 491–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA et al. (2004). Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119: 941–953.

    CAS  PubMed  Google Scholar 

  • Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, Peterson CL . (2006). Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311: 844–847.

    CAS  PubMed  Google Scholar 

  • Shogren-Knaak M, Peterson CL . (2006). Switching on chromatin: mechanistic role of histone H4-K16 acetylation. Cell Cycle 5: 1361–1365.

    CAS  PubMed  Google Scholar 

  • Strahl BD, Allis CD . (2000). The language of covalent histone modifications. Nature 403: 41–45.

    CAS  PubMed  Google Scholar 

  • Tachibana M, Matsumura Y, Fukuda M, Kimura H, Shinkai Y . (2008). G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription. EMBO J 27: 2681–2690.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taipale M, Rea S, Richter K, Vilar A, Lichter P, Imhof A et al. (2005). hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Mol Cell Biol 25: 6798–6810.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tardat M, Murr R, Herceg Z, Sardet C, Julien E . (2007). PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase. J Cell Biol 179: 1413–1426.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tjeertes JV, Miller KM, Jackson SP . (2009). Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 28: 1878–1889.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tryndyak VP, Kovalchuk O, Pogribny IP . (2006). Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins. Cancer Biol Ther 5: 65–70.

    CAS  PubMed  Google Scholar 

  • Turner BM . (2000). Histone acetylation and an epigenetic code. Bioessays 22: 836–845.

    CAS  PubMed  Google Scholar 

  • Turner BM . (2007). Defining an epigenetic code. Nat Cell Biol 9: 2–6.

    CAS  PubMed  Google Scholar 

  • Tzao C, Tung HJ, Jin JS, Sun GH, Hsu HS, Chen BH et al. (2009). Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus. Mod Pathol 22: 252–260.

    CAS  PubMed  Google Scholar 

  • Utley RT, Cote J . (2003). The MYST family of histone acetyltransferases. Curr Top Microbiol Immunol 274: 203–236.

    CAS  PubMed  Google Scholar 

  • Vaissiere T, Sawan C, Herceg Z . (2008). Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res 659: 40–48.

    CAS  PubMed  Google Scholar 

  • Van Den Broeck A, Brambilla E, Moro-Sibilot D, Lantuejoul S, Brambilla C, Eymin B et al. (2008). Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res 14: 7237–7245.

    CAS  PubMed  Google Scholar 

  • van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C et al. (2009). Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet 41: 521–523.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG et al. (2002). The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419: 624–629.

    CAS  PubMed  Google Scholar 

  • Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D . (2010). p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals. J Biol Chem 285: 28553–28564.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vogelauer M, Wu J, Suka N, Grunstein M . (2000). Global histone acetylation and deacetylation in yeast. Nature 408: 495–498.

    CAS  PubMed  Google Scholar 

  • Wagener N, Macher-Goeppinger S, Pritsch M, Husing J, Hoppe-Seyler K, Schirmacher P et al. (2010). Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma. BMC Cancer 10: 524.

    PubMed  PubMed Central  Google Scholar 

  • Wang GG, Song J, Wang Z, Dormann HL, Casadio F, Li H et al. (2009). Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature 459: 847–851.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wei Y, Xia W, Zhang Z, Liu J, Wang H, Adsay NV et al. (2008). Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Mol Carcinog 47: 701–706.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu ZL, Zheng SS, Li ZM, Qiao YY, Aau MY, Yu Q . (2010). Polycomb protein EZH2 regulates E2F1-dependent apoptosis through epigenetically modulating Bim expression. Cell Death Differ 17: 801–810.

    CAS  PubMed  Google Scholar 

  • Xiang Y, Zhu Z, Han G, Lin H, Xu L, Chen CD . (2007). JMJD3 is a histone H3K27 demethylase. Cell Res 17: 850–857.

    CAS  PubMed  Google Scholar 

  • Xu F, Zhang K, Grunstein M . (2005). Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121: 375–385.

    CAS  PubMed  Google Scholar 

  • Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H et al. (2007). PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol Cell 25: 801–812.

    CAS  PubMed  Google Scholar 

  • Yu J, Yu J, Rhodes DR, Tomlins SA, Cao X, Chen G et al. (2007). A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res 67: 10657–10663.

    CAS  PubMed  Google Scholar 

  • Yuan J, Pu M, Zhang Z, Lou Z . (2009). Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8: 1747–1753.

    CAS  PubMed  Google Scholar 

  • Zhao Q, Rank G, Tan YT, Li H, Moritz RL, Simpson RJ et al. (2009). PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat Struct Mol Biol 16: 304–311.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhen L, Gui-lan L, Ping Y, Jin H, Ya-li W . (2010). The expression of H3K9Ac, H3K14Ac, and H4K20TriMe in epithelial ovarian tumors and the clinical significance. Int J Gynecol Cancer 20: 82–86.

    PubMed  Google Scholar 

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Acknowledgements

We apologize to authors whose primary references could not be cited owing to space limitations. JF is supported by a fellowship from Karolinska Institutet Foundations (KID medel). This work was supported by the Swedish Cancer Society, the Swedish Research Council, and the Karolinska Institutet Foundations (KI Cancer).

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  1. Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden

    J Füllgrabe, E Kavanagh & B Joseph

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  1. J Füllgrabe
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Füllgrabe, J., Kavanagh, E. & Joseph, B. Histone onco-modifications. Oncogene 30, 3391–3403 (2011). https://doi.org/10.1038/onc.2011.121

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