Skip to main content
SpringerLink
Log in

Overview of Histone Modification

  • Chapter
  • First Online:
Histone Mutations and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1283))

Abstract

Epigenetics is the epi-information beyond the DNA sequence that can be inherited from parents to offspring. From years of studies, people have found that histone modifications, DNA methylation, and RNA-based mechanism are the main means of epigenetic control. In this chapter, we will focus on the general introductions of epigenetics, which is important in the regulation of chromatin structure and gene expression. With the development and expansion of high-throughput sequencing, various mutations of epigenetic regulators have been identified and proven to be the drivers of tumorigenesis. Epigenetic alterations are used to diagnose individual patients more accurately and specifically. Several drugs, which are targeting epigenetic changes, have been developed to treat patients regarding the awareness of precision medicine. Emerging researches are connecting the epigenetics and cancers together in the molecular mechanism exploration and the development of druggable targets.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Greer EL, Shi Y (2012) Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet 13:343–357

    Article  CAS  Google Scholar 

  5. Murray K (1964) The occurrence of epsilon-N-methyl lysine in histones. Biochemistry 3:10–15

    Article  CAS  Google Scholar 

  6. Black JC, Van Rechem C, Whetstine JR (2012) Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 48:491–507

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Kinkley S, Helmuth J, Polansky JK, Dunkel I, Gasparoni G, Frohler S, Chen W, Walter J, Hamann A, Chung HR (2016) reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells. Nat Commun 7:12514

    Article  CAS  Google Scholar 

  9. Zheng Y, Fornelli L, Compton PD, Sharma S, Canterbury J, Mullen C, Zabrouskov V, Fellers RT, Thomas PM, Licht JD et al (2016) Unabridged analysis of human histone H3 by differential top-down mass spectrometry reveals hypermethylated proteoforms from MMSET/NSD2 overexpression. Mol Cell Proteomics 15:776–790

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39:311–318

    Article  CAS  Google Scholar 

  12. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA, Frampton GM, Sharp PA et al (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 107:21931–21936

    Article  CAS  Google Scholar 

  13. Kim T, Buratowski S (2009) Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5′ transcribed regions. Cell 137:259–272

    Article  CAS  Google Scholar 

  14. Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448:553–560

    Article  CAS  Google Scholar 

  15. Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J, Kouzarides T (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419:407–411

    Article  CAS  Google Scholar 

  16. Zhang B, Zheng H, Huang B, Li W, Xiang Y, Peng X, Ming J, Wu X, Zhang Y, Xu Q et al (2016) Allelic reprogramming of the histone modification H3K4me3 in early mammalian development. Nature 537:553–557

    Article  CAS  Google Scholar 

  17. Briggs SD, Bryk M, Strahl BD, Cheung WL, Davie JK, Dent SY, Winston F, Allis CD (2001) Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Genes Dev 15:3286–3295

    Article  CAS  Google Scholar 

  18. Miller T, Krogan NJ, Dover J, Erdjument-Bromage H, Tempst P, Johnston M, Greenblatt JF, Shilatifard A (2001) COMPASS: a complex of proteins associated with a trithorax-related SET domain protein. Proc Natl Acad Sci U S A 98:12902–12907

    Article  CAS  Google Scholar 

  19. Wang Y, Han Y, Fan E, Zhang K (2015) Analytical strategies used to identify the readers of histone modifications: a review. Anal Chim Acta 891:32–42

    Article  CAS  Google Scholar 

  20. Back F (1976) The variable condition of euchromatin and heterochromatin. Int Rev Cytol 45:25–64

    Article  CAS  Google Scholar 

  21. Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124

    Article  CAS  Google Scholar 

  22. Vavouri T, Lehner B (2012) Human genes with CpG island promoters have a distinct transcription-associated chromatin organization. Genome Biol 13:R110

    Article  Google Scholar 

  23. Towbin BD, Gonzalez-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, Askjaer P, Gasser SM (2012) Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150:934–947

    Article  CAS  Google Scholar 

  24. Rivera C, Saavedra F, Alvarez F, Diaz-Celis C, Ugalde V, Li J, Forne I, Gurard-Levin ZA, Almouzni G, Imhof A et al (2015) Methylation of histone H3 lysine 9 occurs during translation. Nucleic Acids Res 43:9097–9106

    Article  CAS  Google Scholar 

  25. Pinheiro I, Margueron R, Shukeir N, Eisold M, Fritzsch C, Richter FM, Mittler G, Genoud C, Goyama S, Kurokawa M et al (2012) Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150:948–960

    Article  CAS  Google Scholar 

  26. Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H et al (2002) G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev 16:1779–1791

    Article  CAS  Google Scholar 

  27. Rea S, Eisenhaber F, O'Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD et al (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593–599

    Article  CAS  Google Scholar 

  28. Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120

    Article  CAS  Google Scholar 

  29. Salton M, Voss TC, Misteli T (2014) Identification by high-throughput imaging of the histone methyltransferase EHMT2 as an epigenetic regulator of VEGFA alternative splicing. Nucleic Acids Res 42:13662–13673

    Article  CAS  Google Scholar 

  30. Yamada T, Fischle W, Sugiyama T, Allis CD, Grewal SI (2005) The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol Cell 20:173–185

    Article  CAS  Google Scholar 

  31. Banaszynski LA, Wen D, Dewell S, Whitcomb SJ, Lin M, Diaz N, Elsasser SJ, Chapgier A, Goldberg AD, Canaani E et al (2013) Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells. Cell 155:107–120

    Article  CAS  Google Scholar 

  32. Fang J, Feng Q, Ketel CS, Wang H, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Simon JA, Zhang Y (2002) Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol 12:1086–1099

    Article  CAS  Google Scholar 

  33. Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life. Nature 469:343–349

    Article  CAS  Google Scholar 

  34. Simon JA, Kingston RE (2013) Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol Cell 49:808–824

    Article  CAS  Google Scholar 

  35. Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J (2011) A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470:279–283

    Article  CAS  Google Scholar 

  36. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837

    Article  CAS  Google Scholar 

  37. Coward WR, Brand OJ, Pasini A, Jenkins G, Knox AJ, Pang L (2018) Interplay between EZH2 and G9a regulates CXCL10 gene repression in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 58:449–460

    Article  CAS  Google Scholar 

  38. Simon J, Chiang A, Bender W, Shimell MJ, O'Connor M (1993) Elements of the Drosophila bithorax complex that mediate repression by Polycomb group products. Dev Biol 158:131–144

    Article  CAS  Google Scholar 

  39. Mendenhall EM, Koche RP, Truong T, Zhou VW, Issac B, Chi AS, Ku M, Bernstein BE (2010) GC-rich sequence elements recruit PRC2 in mammalian ES cells. PLoS Genet 6:e1001244

    Article  Google Scholar 

  40. Woo CJ, Kharchenko PV, Daheron L, Park PJ, Kingston RE (2010) A region of the human HOXD cluster that confers Polycomb-group responsiveness. Cell 140:99–110

    Article  CAS  Google Scholar 

  41. Kaneko S, Son J, Shen SS, Reinberg D, Bonasio R (2013) PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nat Struct Mol Biol 20:1258–1264

    Article  CAS  Google Scholar 

  42. Kanhere A, Viiri K, Araujo CC, Rasaiyaah J, Bouwman RD, Whyte WA, Pereira CF, Brookes E, Walker K, Bell GW et al (2010) Short RNAs are transcribed from repressed Polycomb target genes and interact with Polycomb repressive complex-2. Mol Cell 38:675–688

    Article  CAS  Google Scholar 

  43. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672

    Article  CAS  Google Scholar 

  44. Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT (2010) Genome-wide identification of Polycomb-associated RNAs by RIP-seq. Mol Cell 40:939–953

    Article  CAS  Google Scholar 

  45. Peng JC, Valouev A, Swigut T, Zhang J, Zhao Y, Sidow A, Wysocka J (2009) Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 139:1290–1302

    Article  Google Scholar 

  46. Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan GC, Lee Y, Orkin SH (2009) Jumonji modulates Polycomb activity and self-renewal versus differentiation of stem cells. Cell 139:1303–1314

    Article  Google Scholar 

  47. Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Bak M, Tommerup N, Rappsilber J, Helin K (2010) JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 464:306–310

    Article  CAS  Google Scholar 

  48. Sanulli S, Justin N, Teissandier A, Ancelin K, Portoso M, Caron M, Michaud A, Lombard B, da Rocha ST, Offer J et al (2015) Jarid2 methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation. Mol Cell 57:769–783

    Article  CAS  Google Scholar 

  49. Son J, Shen SS, Margueron R, Reinberg D (2013) Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin. Genes Dev 27:2663–2677

    Article  CAS  Google Scholar 

  50. Takeuchi T, Watanabe Y, Takano-Shimizu T, Kondo S (2006) Roles of jumonji and jumonji family genes in chromatin regulation and development. Dev Dyn 235:2449–2459

    Article  CAS  Google Scholar 

  51. Kaneko S, Bonasio R, Saldana-Meyer R, Yoshida T, Son J, Nishino K, Umezawa A, Reinberg D (2014) Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol Cell 53:290–300

    Article  CAS  Google Scholar 

  52. Venkatesh S, Li H, Gogol MM, Workman JL (2016) Selective suppression of antisense transcription by Set2-mediated H3K36 methylation. Nat Commun 7:13610

    Article  CAS  Google Scholar 

  53. Carrozza MJ, Li B, Florens L, Suganuma T, Swanson SK, Lee KK, Shia WJ, Anderson S, Yates J, Washburn MP et al (2005) Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123:581–592

    Article  CAS  Google Scholar 

  54. Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C et al (2010) Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell 39:222–233

    Article  CAS  Google Scholar 

  55. Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, Jeltsch A (2010) The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem 285:26114–26120

    Article  CAS  Google Scholar 

  56. Weinberg DN, Papillon-Cavanagh S, Chen H, Yue Y, Chen X, Rajagopalan KN, Horth C, McGuire JT, Xu X, Nikbakht H et al (2019) The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape. Nature 573:281–286

    Article  CAS  Google Scholar 

  57. Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, Xi Y, Park BH, Shi X, Garcia BA et al (2011) NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. Mol Cell 44:609–620

    Article  CAS  Google Scholar 

  58. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B (2011) H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem 286:7983–7989

    Article  CAS  Google Scholar 

  59. Sen P, Dang W, Donahue G, Dai J, Dorsey J, Cao X, Liu W, Cao K, Perry R, Lee JY et al (2015) H3K36 methylation promotes longevity by enhancing transcriptional fidelity. Genes Dev 29:1362–1376

    Article  CAS  Google Scholar 

  60. Suzuki S, Kato H, Suzuki Y, Chikashige Y, Hiraoka Y, Kimura H, Nagao K, Obuse C, Takahata S, Murakami Y (2016) Histone H3K36 trimethylation is essential for multiple silencing mechanisms in fission yeast. Nucleic Acids Res 44:4147–4162

    Article  CAS  Google Scholar 

  61. Morselli M, Pastor WA, Montanini B, Nee K, Ferrari R, Fu K, Bonora G, Rubbi L, Clark AT, Ottonello S et al (2015) In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse. elife 4:e06205

    Article  Google Scholar 

  62. Barash Y, Calarco JA, Gao W, Pan Q, Wang X, Shai O, Blencowe BJ, Frey BJ (2010) Deciphering the splicing code. Nature 465:53–59

    Article  CAS  Google Scholar 

  63. Matlin AJ, Clark F, Smith CW (2005) Understanding alternative splicing: towards a cellular code. Nat Rev Mol Cell Biol 6:386–398

    Article  CAS  Google Scholar 

  64. Wang Z, Burge CB (2008) Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14:802–813

    Article  CAS  Google Scholar 

  65. Li F, Mao G, Tong D, Huang J, Gu L, Yang W, Li GM (2013) The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha. Cell 153:590–600

    Article  CAS  Google Scholar 

  66. Huang H, Weng H, Zhou K, Wu T, Zhao BS, Sun M, Chen Z, Deng X, Xiao G, Auer F et al (2019) Histone H3 trimethylation at lysine 36 guides m(6)a RNA modification co-transcriptionally. Nature 567:414–419

    Article  CAS  Google Scholar 

  67. Kizer KO, Phatnani HP, Shibata Y, Hall H, Greenleaf AL, Strahl BD (2005) A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol Cell Biol 25:3305–3316

    Article  CAS  Google Scholar 

  68. Eram MS, Bustos SP, Lima-Fernandes E, Siarheyeva A, Senisterra G, Hajian T, Chau I, Duan S, Wu H, Dombrovski L et al (2014) Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 protein. J Biol Chem 289:12177–12188

    Article  CAS  Google Scholar 

  69. Nguyen AT, Zhang Y (2011) The diverse functions of Dot1 and H3K79 methylation. Genes Dev 25:1345–1358

    Article  CAS  Google Scholar 

  70. Jones B, Su H, Bhat A, Lei H, Bajko J, Hevi S, Baltus GA, Kadam S, Zhai H, Valdez R et al (2008) The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet 4:e1000190

    Article  Google Scholar 

  71. Singer MS, Kahana A, Wolf AJ, Meisinger LL, Peterson SE, Goggin C, Mahowald M, Gottschling DE (1998) Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics 150:613–632

    Article  CAS  Google Scholar 

  72. Ng HH, Xu RM, Zhang Y, Struhl K (2002) Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J Biol Chem 277:34655–34657

    Article  CAS  Google Scholar 

  73. McGinty RK, Kim J, Chatterjee C, Roeder RG, Muir TW (2008) Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation. Nature 453:812–816

    Article  CAS  Google Scholar 

  74. Altaf M, Utley RT, Lacoste N, Tan S, Briggs SD, Cote J (2007) Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin. Mol Cell 28:1002–1014

    Article  CAS  Google Scholar 

  75. Huyen Y, Zgheib O, Ditullio RA Jr, Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS, Stavridi ES, Halazonetis TD (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432:406–411

    Article  CAS  Google Scholar 

  76. Mueller D, Bach C, Zeisig D, Garcia-Cuellar MP, Monroe S, Sreekumar A, Zhou R, Nesvizhskii A, Chinnaiyan A, Hess JL et al (2007) A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 110:4445–4454

    Article  CAS  Google Scholar 

  77. Sato Y, Kujirai T, Arai R, Asakawa H, Ohtsuki C, Horikoshi N, Yamagata K, Ueda J, Nagase T, Haraguchi T et al (2016) A genetically encoded probe for live-cell imaging of H4K20 monomethylation. J Mol Biol 428:3885–3902

    Article  CAS  Google Scholar 

  78. Kuo AJ, Song J, Cheung P, Ishibe-Murakami S, Yamazoe S, Chen JK, Patel DJ, Gozani O (2012) The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature 484:115–119

    Article  CAS  Google Scholar 

  79. Boccuni P, MacGrogan D, Scandura JM, Nimer SD (2003) The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6). J Biol Chem 278:15412–15420

    Article  CAS  Google Scholar 

  80. Jorgensen S, Schotta G, Sorensen CS (2013) Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity. Nucleic Acids Res 41:2797–2806

    Article  CAS  Google Scholar 

  81. Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G (2006) Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127:1361–1373

    Article  CAS  Google Scholar 

  82. Lu X, Simon MD, Chodaparambil JV, Hansen JC, Shokat KM, Luger K (2008) The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure. Nat Struct Mol Biol 15:1122–1124

    Article  CAS  Google Scholar 

  83. Tardat M, Brustel J, Kirsh O, Lefevbre C, Callanan M, Sardet C, Julien E (2010) The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells. Nat Cell Biol 12:1086–1093

    Article  CAS  Google Scholar 

  84. Yang H, Kwon CS, Choi Y, Lee D (2016) Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast. Biochem Biophys Res Commun 476:515–521

    Article  CAS  Google Scholar 

  85. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395

    Article  CAS  Google Scholar 

  86. Clayton AL, Hebbes TR, Thorne AW, Crane-Robinson C (1993) Histone acetylation and gene induction in human cells. FEBS Lett 336:23–26

    Article  CAS  Google Scholar 

  87. Pogo BG, Allfrey VG, Mirsky AE (1966) RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc Natl Acad Sci U S A 55:805–812

    Article  CAS  Google Scholar 

  88. Yang XJ, Seto E (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31:449–461

    Article  CAS  Google Scholar 

  89. Seto E, Yoshida M (2014) Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Perspect Biol 6:a018713

    Article  Google Scholar 

  90. Lombardi PM, Cole KE, Dowling DP, Christianson DW (2011) Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes. Curr Opin Struct Biol 21:735–743

    Article  CAS  Google Scholar 

  91. Vaquero A, Sternglanz R, Reinberg D (2007) NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs. Oncogene 26:5505–5520

    Article  CAS  Google Scholar 

  92. Bose P, Dai Y, Grant S (2014) Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights. Pharmacol Ther 143:323–336

    Article  CAS  Google Scholar 

  93. Suraweera A, O'Byrne KJ, Richard DJ (2018) Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front Oncol 8:92

    Article  Google Scholar 

  94. Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E, Gregory L, Lonie L, Chew A, Wei CL et al (2010) Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 32:317–328

    Article  CAS  Google Scholar 

  95. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW et al (2009) Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459:108–112

    Article  CAS  Google Scholar 

  96. Khan A, Zhang X (2016) dbSUPER: a database of super-enhancers in mouse and human genome. Nucleic Acids Res 44:D164–D171

    Article  CAS  Google Scholar 

  97. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA (2013) Super-enhancers in the control of cell identity and disease. Cell 155:934–947

    Article  CAS  Google Scholar 

  98. Bannister AJ, Kouzarides T (1996) The CBP co-activator is a histone acetyltransferase. Nature 384:641–643

    Article  CAS  Google Scholar 

  99. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y (1996) The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87:953–959

    Article  CAS  Google Scholar 

  100. Giles RH, Peters DJ, Breuning MH (1998) Conjunction dysfunction: CBP/p300 in human disease. Trends Genet 14:178–183

    Article  CAS  Google Scholar 

  101. Wang GG, Allis CD, Chi P (2007) Chromatin remodeling and cancer, part I: covalent histone modifications. Trends Mol Med 13:363–372

    Article  CAS  Google Scholar 

  102. Kung AL, Rebel VI, Bronson RT, Ch'ng LE, Sieff CA, Livingston DM, Yao TP (2000) Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev 14:272–277

    Article  CAS  Google Scholar 

  103. Josling GA, Selvarajah SA, Petter M, Duffy MF (2012) The role of bromodomain proteins in regulating gene expression. Genes (Basel) 3:320–343

    Article  CAS  Google Scholar 

  104. Taniguchi Y (2016) The bromodomain and extra-terminal domain (BET) family: functional anatomy of BET paralogous proteins. Int J Mol Sci 17:1849

    Article  Google Scholar 

  105. Benton CB, Fiskus W, Bhalla KN (2017) Targeting histone acetylation: readers and writers in leukemia and cancer. Cancer J 23:286–291

    Article  CAS  Google Scholar 

  106. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102:15545–15550

    Article  CAS  Google Scholar 

  107. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I et al (2010) Selective inhibition of BET bromodomains. Nature 468:1067–1073

    Article  CAS  Google Scholar 

  108. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA (2013) Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153:320–334

    Article  CAS  Google Scholar 

  109. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J et al (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 146:904–917

    Article  CAS  Google Scholar 

  110. Andrieu G, Belkina AC, Denis GV (2016) Clinical trials for BET inhibitors run ahead of the science. Drug Discov Today Technol 19:45–50

    Article  Google Scholar 

  111. North JA, Simon M, Ferdinand MB, Shoffner MA, Picking JW, Howard CJ, Mooney AM, van Noort J, Poirier MG, Ottesen JJ (2014) Histone H3 phosphorylation near the nucleosome dyad alters chromatin structure. Nucleic Acids Res 42:4922–4933

    Article  CAS  Google Scholar 

  112. Cohen P (1989) The structure and regulation of protein phosphatases. Annu Rev Biochem 58:453–508

    Article  CAS  Google Scholar 

  113. Sawicka A, Seiser C (2014) Sensing core histone phosphorylation - a matter of perfect timing. Biochim Biophys Acta 1839:711–718

    Article  CAS  Google Scholar 

  114. Fischle W, Tseng BS, Dormann HL, Ueberheide BM, Garcia BA, Shabanowitz J, Hunt DF, Funabiki H, Allis CD (2005) Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438:1116–1122

    Article  CAS  Google Scholar 

  115. Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalli T, Brinkley BR, Bazett-Jones DP, Allis CD (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 106:348–360

    Article  CAS  Google Scholar 

  116. Hirota T, Lipp JJ, Toh BH, Peters JM (2005) Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438:1176–1180

    Article  CAS  Google Scholar 

  117. Vagnarelli P, Hudson DF, Ribeiro SA, Trinkle-Mulcahy L, Spence JM, Lai F, Farr CJ, Lamond AI, Earnshaw WC (2006) Condensin and repo-man-PP1 co-operate in the regulation of chromosome architecture during mitosis. Nat Cell Biol 8:1133–1142

    Article  CAS  Google Scholar 

  118. Momany M, Taylor I (2000) Landmarks in the early duplication cycles of Aspergillus fumigatus and Aspergillus nidulans: polarity, germ tube emergence and septation. Microbiology 146(Pt 12):3279–3284

    Article  CAS  Google Scholar 

  119. Kaneko S, Li G, Son J, Xu CF, Margueron R, Neubert TA, Reinberg D (2010) Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev 24:2615–2620

    Article  CAS  Google Scholar 

  120. Zhu X, Li D, Zhang Z, Zhu W, Li W, Zhao J, Xing X, He Z, Wang S, Wang F et al (2017) Persistent phosphorylation at specific H3 serine residues involved in chemical carcinogen-induced cell transformation. Mol Carcinog 56:1449–1460

    Article  CAS  Google Scholar 

  121. Wang F, Dai J, Daum JR, Niedzialkowska E, Banerjee B, Stukenberg PT, Gorbsky GJ, Higgins JM (2010) Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330:231–235

    Article  CAS  Google Scholar 

  122. Yamagishi Y, Honda T, Tanno Y, Watanabe Y (2010) Two histone marks establish the inner centromere and chromosome bi-orientation. Science 330:239–243

    Article  CAS  Google Scholar 

  123. Suzuki T, Watanabe H, Kita K, Honma T, Ochi T (2018) Arsenite-induced histone H3 modification and its effects on EGR1 and FOS expression in HeLa cells. J Appl Toxicol 38:734–743

    Article  CAS  Google Scholar 

  124. Preuss U, Landsberg G, Scheidtmann KH (2003) Novel mitosis-specific phosphorylation of histone H3 at Thr11 mediated by Dlk/ZIP kinase. Nucleic Acids Res 31:878–885

    Article  CAS  Google Scholar 

  125. Yamashita Y (2009) Asymmetric stem cell division and pathology: insights from Drosophila stem cell systems. J Pathol 217:181–185

    Article  CAS  Google Scholar 

  126. Tran V, Lim C, Xie J, Chen X (2012) Asymmetric division of Drosophila male germline stem cell shows asymmetric histone distribution. Science 338:679–682

    Article  CAS  Google Scholar 

  127. Xie J, Wooten M, Tran V, Chen BC, Pozmanter C, Simbolon C, Betzig E, Chen X (2015) Histone H3 threonine phosphorylation regulates asymmetric histone inheritance in the Drosophila male germline. Cell 163:920–933

    Article  CAS  Google Scholar 

  128. Wegel E, Shaw P (2005) Gene activation and deactivation related changes in the three-dimensional structure of chromatin. Chromosoma 114:331–337

    Article  Google Scholar 

  129. Burns LG, Peterson CL (1997) Protein complexes for remodeling chromatin. Biochim Biophys Acta 1350:159–168

    Article  CAS  Google Scholar 

  130. Zhou CY, Johnson SL, Gamarra NI, Narlikar GJ (2016) Mechanisms of ATP-dependent chromatin remodeling motors. Annu Rev Biophys 45:153–181

    Article  CAS  Google Scholar 

  131. Cote J, Quinn J, Workman JL, Peterson CL (1994) Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science 265:53–60

    Article  CAS  Google Scholar 

  132. Collingwood TN, Urnov FD, Wolffe AP (1999) Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription. J Mol Endocrinol 23:255–275

    Article  CAS  Google Scholar 

  133. Awad S, Hassan AH (2008) The Swi2/Snf2 bromodomain is important for the full binding and remodeling activity of the SWI/SNF complex on H3- and H4-acetylated nucleosomes. Ann N Y Acad Sci 1138:366–375

    Article  CAS  Google Scholar 

  134. Deuring R, Fanti L, Armstrong JA, Sarte M, Papoulas O, Prestel M, Daubresse G, Verardo M, Moseley SL, Berloco M et al (2000) The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo. Mol Cell 5:355–365

    Article  CAS  Google Scholar 

  135. Tyagi M, Imam N, Verma K, Patel AK (2016) Chromatin remodelers: we are the drivers!! Nucleus 7:388–404

    Article  CAS  Google Scholar 

  136. Grune T, Brzeski J, Eberharter A, Clapier CR, Corona DF, Becker PB, Muller CW (2003) Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI. Mol Cell 12:449–460

    Article  Google Scholar 

  137. Klement K, Luijsterburg MS, Pinder JB, Cena CS, Del Nero V, Wintersinger CM, Dellaire G, van Attikum H, Goodarzi AA (2014) Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair. J Cell Biol 207:717–733

    Article  CAS  Google Scholar 

  138. Andersen EC, Lu X, Horvitz HR (2006) C. elegans ISWI and NURF301 antagonize an Rb-like pathway in the determination of multiple cell fates. Development 133:2695–2704

    Article  CAS  Google Scholar 

  139. Pray-Grant MG, Daniel JA, Schieltz D, Yates JR 3rd, Grant PA (2005) Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation. Nature 433:434–438

    Article  CAS  Google Scholar 

  140. Sims RJ 3rd, Chen CF, Santos-Rosa H, Kouzarides T, Patel SS, Reinberg D (2005) Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains. J Biol Chem 280:41789–41792

    Article  CAS  Google Scholar 

  141. Stokes DG, Perry RP (1995) DNA-binding and chromatin localization properties of CHD1. Mol Cell Biol 15:2745–2753

    Article  CAS  Google Scholar 

  142. Musselman CA, Mansfield RE, Garske AL, Davrazou F, Kwan AH, Oliver SS, O’Leary H, Denu JM, Mackay JP, Kutateladze TG (2009) Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. Biochem J 423:179–187

    Article  CAS  Google Scholar 

  143. Allen MD, Religa TL, Freund SM, Bycroft M (2007) Solution structure of the BRK domains from CHD7. J Mol Biol 371:1135–1140

    Article  CAS  Google Scholar 

  144. Falbo KB, Alabert C, Katou Y, Wu S, Han J, Wehr T, Xiao J, He X, Zhang Z, Shi Y et al (2009) Involvement of a chromatin remodeling complex in damage tolerance during DNA replication. Nat Struct Mol Biol 16:1167–1172

    Article  CAS  Google Scholar 

  145. Papamichos-Chronakis M, Watanabe S, Rando OJ, Peterson CL (2011) Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity. Cell 144:200–213

    Article  CAS  Google Scholar 

  146. Mizuguchi G, Shen X, Landry J, Wu WH, Sen S, Wu C (2004) ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex. Science 303:343–348

    Article  CAS  Google Scholar 

  147. Papamichos-Chronakis M, Krebs JE, Peterson CL (2006) Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage. Genes Dev 20:2437–2449

    Article  CAS  Google Scholar 

  148. Gangaraju VK, Bartholomew B (2007) Mechanisms of ATP dependent chromatin remodeling. Mutat Res 618:3–17

    Article  CAS  Google Scholar 

  149. Yan L, Wang L, Tian Y, Xia X, Chen Z (2016) Structure and regulation of the chromatin remodeller ISWI. Nature 540:466–469

    Article  CAS  Google Scholar 

  150. March-Diaz R, Reyes JC (2009) The beauty of being a variant: H2A.Z and the SWR1 complex in plants. Mol Plant 2:565–577

    Article  CAS  Google Scholar 

  151. van Attikum H, Fritsch O, Gasser SM (2007) Distinct roles for SWR1 and INO80 chromatin remodeling complexes at chromosomal double-strand breaks. EMBO J 26:4113–4125

    Article  Google Scholar 

  152. Konev AY, Tribus M, Park SY, Podhraski V, Lim CY, Emelyanov AV, Vershilova E, Pirrotta V, Kadonaga JT, Lusser A et al (2007) CHD1 motor protein is required for deposition of histone variant H3.3 into chromatin in vivo. Science 317:1087–1090

    Article  CAS  Google Scholar 

  153. Narlikar GJ, Sundaramoorthy R, Owen-Hughes T (2013) Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes. Cell 154:490–503

    Article  CAS  Google Scholar 

  154. Cui K, Tailor P, Liu H, Chen X, Ozato K, Zhao K (2004) The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming. Mol Cell Biol 24:4476–4486

    Article  CAS  Google Scholar 

  155. Garcia-Pedrero JM, Kiskinis E, Parker MG, Belandia B (2006) The SWI/SNF chromatin remodeling subunit BAF57 is a critical regulator of estrogen receptor function in breast cancer cells. J Biol Chem 281:22656–22664

    Article  CAS  Google Scholar 

  156. Hodges C, Kirkland JG, Crabtree GR (2016) The many roles of BAF (mSWI/SNF) and PBAF complexes in cancer. Cold Spring Harb Perspect Med 6:a026930

    Article  Google Scholar 

  157. Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, Maitra A, Pollack JR (2012) Convergent structural alterations define SWItch/sucrose non fermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer. Proc Natl Acad Sci U S A 109:E252–E259

    Article  CAS  Google Scholar 

  158. Vries RG, Bezrookove V, Zuijderduijn LM, Kia SK, Houweling A, Oruetxebarria I, Raap AK, Verrijzer CP (2005) Cancer-associated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint. Genes Dev 19:665–670

    Article  CAS  Google Scholar 

  159. Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T et al (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203–207

    Article  CAS  Google Scholar 

  160. Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199–202

    Article  Google Scholar 

  161. Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE, Perkins EM, Hur JK, Aravin AA, Toth KF (2013) Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 27:390–399

    Article  Google Scholar 

  162. Derrien T, Guigo R, Johnson R (2011) The long non-coding RNAs: a new (P)layer in the “dark matter”. Front Genet 2:107

    Google Scholar 

  163. Szczesniak MW, Makalowska I (2016) lncRNA-RNA interactions across the human transcriptome. PLoS One 11:e0150353

    Article  Google Scholar 

  164. Wan G, Hu X, Liu Y, Han C, Sood AK, Calin GA, Zhang X, Lu X (2013) A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4 acetylation. EMBO J 32:2833–2847

    Article  CAS  Google Scholar 

  165. Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res 67:3963–3969

    Article  CAS  Google Scholar 

  166. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38:662–674

    Article  CAS  Google Scholar 

  167. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323

    Article  CAS  Google Scholar 

  168. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693

    Article  CAS  Google Scholar 

  169. Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA et al (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–124

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Life Sciences Institute, Zhejiang University, Hangzhou, P.R. China

    Yanjun Zhang, Zhongxing Sun, Junqi Jia, Tianjiao Du, Nachuan Zhang, Yin Tang, Yuan Fang & Dong Fang

Authors
  1. Yanjun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhongxing Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junqi Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tianjiao Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nachuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuan Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dong Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dong Fang .

Editor information

Editors and Affiliations

  1. Institute of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China

    Dong Fang

  2. State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China

    Junhong Han

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zhang, Y. et al. (2021). Overview of Histone Modification. In: Fang, D., Han, J. (eds) Histone Mutations and Cancer. Advances in Experimental Medicine and Biology, vol 1283. Springer, Singapore. https://doi.org/10.1007/978-981-15-8104-5_1

Download citation

Publish with us

Policies and ethics

Search

Navigation