Skip to main content

Advertisement

SpringerLink
Log in

The significance, development and progress of high-throughput combinatorial histone code analysis

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The physiological state of eukaryotic DNA is chromatin. Nucleosomes, which consist of DNA in complex with histones, are the fundamental unit of chromatin. The post-translational modifications (PTMs) of histones play a critical role in the control of gene transcription, epigenetics and other DNA-templated processes. It has been known for several years that these PTMs function in concert to allow for the storage and transduction of highly specific signals through combinations of modifications. This code, the combinatorial histone code, functions much like a bar code or combination lock providing the potential for massive information content. The capacity to directly measure these combinatorial histone codes has mostly been laborious and challenging, thus limiting efforts often to one or two samples. Recently, progress has been made in determining such information quickly, quantitatively and sensitively. Here we review both the historical and recent progress toward routine and rapid combinatorial histone code analysis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. 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(6648):251–260

    CAS  PubMed  Google Scholar 

  2. Prohaska SJ, Stadler PF, Krakauer DC (2010) Innovation in gene regulation: the case of chromatin computation. J Theor Biol 265(1):27–44

    CAS  PubMed  Google Scholar 

  3. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080

    CAS  PubMed  Google Scholar 

  4. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403(6765):41–45

    CAS  PubMed  Google Scholar 

  5. Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705

    CAS  PubMed  Google Scholar 

  6. Turner BM (2002) Cellular memory and the histone code. Cell 111(3):285–291

    CAS  PubMed  Google Scholar 

  7. Allis CD, Jenuwein T, Reinberg D (2007) Overview and concepts. In: Allis CD, Jenuwein T, Reinberg D, Caparros ML (eds) Epigenetics. Cold Spring Harbor Press, Cold Spring Harbor, pp 44–52

    Google Scholar 

  8. Iizuka M, Smith MM (2003) Functional consequences of histone modifications. Curr Opin Genet Dev 13(2):154–160

    CAS  PubMed  Google Scholar 

  9. Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31(1):27–36

    CAS  PubMed  Google Scholar 

  10. Suganuma T, Workman JL (2008) Crosstalk among histone modifications. Cell 135(4):604–607

    CAS  PubMed  Google Scholar 

  11. Park PJ (2009) ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 10(10):669–680

    CAS  PubMed  Google Scholar 

  12. Barlesi F, Giaccone G, Gallegos-Ruiz MI, Loundou A, Span SW, Lefesvre P, Kruyt FA, Rodriguez JA (2007) Global histone modifications predict prognosis of resected non small-cell lung cancer. J Clin Oncol 25(28):4358–4364

    PubMed  Google Scholar 

  13. Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM, Soria D, Garibaldi JM, Paish CE, Ammar AA, Grainge MJ, Ball GR, Abdelghany MK, Martinez-Pomares L, Heery DM, Ellis IO (2009) Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res 69(9):3802–3809

    CAS  PubMed  Google Scholar 

  14. Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK (2009) Global levels of histone modifications predict prognosis in different cancers. Am J Pathol 174(5):1619–1628

    CAS  PubMed  Google Scholar 

  15. Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK (2005) Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435(7046):1262–1266

    CAS  PubMed  Google Scholar 

  16. Dion MF, Altschuler SJ, Wu LF, Rando OJ (2005) Genomic characterization reveals a simple histone H4 acetylation code. Proc Natl Acad Sci USA 102(15):5501–5506

    CAS  PubMed  Google Scholar 

  17. Liu CL, Kaplan T, Kim M, Buratowski S, Schreiber SL, Friedman N, Rando OJ (2005) Single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol 3(10):e328

    PubMed  Google Scholar 

  18. Kurdistani SK, Tavazoie S, Grunstein M (2004) Mapping global histone acetylation patterns to gene expression. Cell 117(6):721–733

    CAS  PubMed  Google Scholar 

  19. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40(7):897–903

    CAS  PubMed  Google Scholar 

  20. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125(2):315–326

    CAS  PubMed  Google Scholar 

  21. Greaves IK, Rangasamy D, Ridgway P, Tremethick DJ (2007) H2A.Z contributes to the unique 3D structure of the centromere. Proc Natl Acad Sci USA 104(2):525–530

    CAS  PubMed  Google Scholar 

  22. 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(7):1968–1976

    PubMed  Google Scholar 

  23. Jiang L, Smith JN, Anderson SL, Ma P, Mizzen CA, Kelleher NL (2007) Global assessment of combinatorial post-translational modification of core histones in yeast using contemporary mass spectrometry. LYS4 trimethylation correlates with degree of acetylation on the same H3 tail. J Biol Chem 282(38):27923–27934

    CAS  PubMed  Google Scholar 

  24. Markaki Y, Christogianni A, Politou AS, Georgatos SD (2009) Phosphorylation of histone H3 at Thr3 is part of a combinatorial pattern that marks and configures mitotic chromatin. J Cell Sci 122(Pt 16):2809–2819

    CAS  PubMed  Google Scholar 

  25. Kang TJ, Yuzawa S, Suga H (2008) Expression of histone H3 tails with combinatorial lysine modifications under the reprogrammed genetic code for the investigation on epigenetic markers. Chem Biol 15(11):1166–1174

    CAS  PubMed  Google Scholar 

  26. Kirmizis A, Santos-Rosa H, Penkett CJ, Singer MA, Vermeulen M, Mann M, Bahler J, Green RD, Kouzarides T (2007) Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation. Nature 449(7164):928–932

    CAS  PubMed  Google Scholar 

  27. Taverna SD, Ilin S, Rogers RS, Tanny JC, Lavender H, Li H, Baker L, Boyle J, Blair LP, Chait BT, Patel DJ, Aitchison JD, Tackett AJ, Allis CD (2006) Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs. Mol Cell 24(5):785–796

    CAS  PubMed  Google Scholar 

  28. Hung T, Binda O, Champagne KS, Kuo AJ, Johnson K, Chang HY, Simon MD, Kutateladze TG, Gozani O (2009) ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation. Mol Cell 33(2):248–256

    CAS  PubMed  Google Scholar 

  29. 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(7071):1116–1122

    CAS  PubMed  Google Scholar 

  30. Daujat S, Zeissler U, Waldmann T, Happel N, Schneider R (2005) HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding. J Biol Chem 280(45):38090–38095

    CAS  PubMed  Google Scholar 

  31. Garske AL, Craciun G, Denu JM (2008) A combinatorial H4 tail library for exploring the histone code. Biochemistry 47(31):8094–8102

    CAS  PubMed  Google Scholar 

  32. Li B, Gogol M, Carey M, Lee D, Seidel C, Workman JL (2007) Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science 316(5827):1050–1054

    CAS  PubMed  Google Scholar 

  33. Saksouk N, Avvakumov N, Champagne KS, Hung T, Doyon Y, Cayrou C, Paquet E, Ullah M, Landry AJ, Cote V, Yang XJ, Gozani O, Kutateladze TG, Cote J (2009) HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail. Mol Cell 33(2):257–265

    CAS  PubMed  Google Scholar 

  34. Moriniere J, Rousseaux S, Steuerwald U, Soler-Lopez M, Curtet S, Vitte AL, Govin J, Gaucher J, Sadoul K, Hart DJ, Krijgsveld J, Khochbin S, Muller CW, Petosa C (2009) Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. Nature 461(7264):664–668

    CAS  PubMed  Google Scholar 

  35. Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P, Lee D, Erdjument-Bromage H, Tempst P, Nimer SD, Wang YH, Reinberg D (2007) L3MBTL1, a histone-methylation-dependent chromatin lock. Cell 129(5):915–928

    CAS  PubMed  Google Scholar 

  36. Ruthenburg AJ, Li H, Patel DJ, Allis CD (2007) Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 8(12):983–994

    CAS  PubMed  Google Scholar 

  37. Sims JK, Houston SI, Magazinnik T, Rice JC (2006) A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. J Biol Chem 281(18):12760–12766

    CAS  PubMed  Google Scholar 

  38. Campos EI, Reinberg D (2009) Histones: annotating chromatin. Annu Rev Genet 43:559–599

    CAS  PubMed  Google Scholar 

  39. Briggs SD, Xiao T, Sun ZW, Caldwell JA, Shabanowitz J, Hunt DF, Allis CD, Strahl BD (2002) Gene silencing: trans-histone regulatory pathway in chromatin. Nature 418(6897):498

    CAS  PubMed  Google Scholar 

  40. Lee JS, Shukla A, Schneider J, Swanson SK, Washburn MP, Florens L, Bhaumik SR, Shilatifard A (2007) Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS. Cell 131(6):1084–1096

    CAS  PubMed  Google Scholar 

  41. Du LL, Nakamura TM, Russell P (2006) Histone modification-dependent and -independent pathways for recruitment of checkpoint protein Crb2 to double-strand breaks. Genes Dev 20(12):1583–1596

    CAS  PubMed  Google Scholar 

  42. 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(7015):406–411

    CAS  PubMed  Google Scholar 

  43. Neelin JM, Connell GE (1959) Zone electrophoresis of chicken-erythrocyte histone in starch gel. Biochim Biophys Acta 31(2):539–541

    CAS  PubMed  Google Scholar 

  44. Panyim S, Chalkley R (1969) High resolution acrylamide gel electrophoresis of histones. Arch Biochem Biophys 130(1):337–346

    CAS  PubMed  Google Scholar 

  45. Franklin SG, Zweidler A (1977) Non-allelic variants of histones 2a, 2b and 3 in mammals. Nature 266(5599):273–275

    CAS  PubMed  Google Scholar 

  46. Bonner WM, West MH, Stedman JD (1980) Two-dimensional gel analysis of histones in acid extracts of nuclei, cells, and tissues. Eur J Biochem 109(1):17–23

    CAS  PubMed  Google Scholar 

  47. Gurley LR, London JE, Valdez JG (1991) High-performance capillary electrophoresis of histones. J Chromatogr 559(1–2):431–443

    CAS  PubMed  Google Scholar 

  48. Lindner H, Helliger W, Dirschlmayer A, Jaquemar M, Puschendorf B (1992) High-performance capillary electrophoresis of core histones and their acetylated modified derivatives. Biochem J 283(Pt 2):467–471

    CAS  PubMed  Google Scholar 

  49. Lindner H, Helliger W, Dirschlmayer A, Talasz H, Wurm M, Sarg B, Jaquemar M, Puschendorf B (1992) Separation of phosphorylated histone H1 variants by high-performance capillary electrophoresis. J Chromatogr 608(1–2):211–216

    CAS  PubMed  Google Scholar 

  50. Lindner H, Helliger W, Sarg B, Meraner C (1995) Effect of buffer composition on the migration order and separation of histone H1 subtypes. Electrophoresis 16(4):604–610

    CAS  PubMed  Google Scholar 

  51. Lindner H, Wurm M, Dirschlmayer A, Sarg B, Helliger W (1993) Application of high-performance capillary electrophoresis to the analysis of H1 histones. Electrophoresis 14(5–6):480–485

    CAS  PubMed  Google Scholar 

  52. Aguilar C, Hofte AJ, Tjaden UR, van der Greef J (2001) Analysis of histones by on-line capillary zone electrophoresis–electrospray ionisation mass spectrometry. J Chromatogr A 926(1):57–67

    CAS  PubMed  Google Scholar 

  53. Wiktorowicz JE, Colburn JC (1990) Separation of cationic proteins via charge reversal in capillary electrophoresis. Electrophoresis 11(9):769–773

    CAS  PubMed  Google Scholar 

  54. Mizzen CA, McLachlan DR (2000) Capillary electrophoresis of histone H1 variants at neutral pH in dynamically modified fused-silica tubing. Electrophoresis 21(12):2359–2367

    CAS  PubMed  Google Scholar 

  55. Garcia BA, Hake SB, Diaz RL, Kauer M, Morris SA, Recht J, Shabanowitz J, Mishra N, Strahl BD, Allis CD, Hunt DF (2007) Organismal differences in post-translational modifications in histones H3 and H4. J Biol Chem 282(10):7641–7655

    CAS  PubMed  Google Scholar 

  56. Garcia BA, Pesavento JJ, Mizzen CA, Kelleher NL (2007) Pervasive combinatorial modification of histone H3 in human cells. Nat Methods 4(6):487–489

    CAS  PubMed  Google Scholar 

  57. Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF (2006) Expression patterns and post-translational modifications associated with mammalian histone H3 variants. J Biol Chem 281(1):559–568

    CAS  PubMed  Google Scholar 

  58. Hake SB, Garcia BA, Kauer M, Baker SP, Shabanowitz J, Hunt DF, Allis CD (2005) Serine 31 phosphorylation of histone variant H3.3 is specific to regions bordering centromeres in metaphase chromosomes. Proc Natl Acad Sci USA 102(18):6344–6349

    CAS  PubMed  Google Scholar 

  59. Certa U, von Ehrenstein G (1981) Reversed-phase high-performance liquid chromatography of histones. Anal Biochem 118(1):147–154

    CAS  PubMed  Google Scholar 

  60. D’Anna JA, Thayer MM, Tobey RA, Gurley LR (1985) G1- and S-phase syntheses of histones H1 and H1o in mitotically selected CHO cells: utilization of high-performance liquid chromatography. Biochemistry 24(8):2005–2010

    PubMed  Google Scholar 

  61. Gurley LR, D’Anna JA, Blumenfeld M, Valdez JG, Sebring RJ, Donahue PR, Prentice DA, Spall WD (1984) Preparation of histone variants and high-mobility group proteins by reversed-phase high-performance liquid chromatography. J Chromatogr 297:147–165

    CAS  PubMed  Google Scholar 

  62. Gurley LR, Prentice DA, Valdez JG, Spall WD (1983) Histone fractionation by high-performance liquid chromatography on cyanoalkysilane (CN) reverse-phase columns. Anal Biochem 131(2):465–477

    CAS  PubMed  Google Scholar 

  63. Gurley LR, Prentice DA, Valdez JG, Spall WD (1983) High-performance liquid chromatography of chromatin histones. J Chromatogr 266:609–627

    CAS  PubMed  Google Scholar 

  64. Lindner H, Helliger W, Puschendorf B (1986) Histone separation by high-performance liquid chromatography on C4 reverse-phase columns. Anal Biochem 158(2):424–430

    CAS  PubMed  Google Scholar 

  65. Lindner H, Helliger W, Puschendorf B (1988) Separation of Friend erythroleukaemic cell histones and high-mobility-group proteins by reversed-phase high-performance liquid chromatography. J Chromatogr 450(3):309–316

    CAS  PubMed  Google Scholar 

  66. Helliger W, Lindner H, Hauptlorenz S, Puschendorf B (1988) A new HPLC isolation procedure for chicken and goose erythrocyte histones. Biochem J 255(1):23–27

    CAS  PubMed  Google Scholar 

  67. Lindner H, Helliger W, Puschendorf B (1990) Separation of rat tissue histone H1 subtypes by reverse-phase HPLC Identification and assignment to a standard H1 nomenclature. Biochem J 269(2):359–363

    CAS  PubMed  Google Scholar 

  68. Lindner H, Wesierska-Gadek J, Helliger W, Puschendorf B, Sauermann G (1989) Identification of ADP-ribosylated histones by the combined use of high-performance liquid chromatography and electrophoresis. J Chromatogr 472(1):243–249

    CAS  PubMed  Google Scholar 

  69. Neelin JM, Butler GC (1959) The fractionation of the histones of calf thymus and chicken erythrocytes by cation-exchange chromatography with sodium salts. Can J Biochem Physiol 37(7):843–859

    CAS  PubMed  Google Scholar 

  70. Alpert AJ (1990) Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. J Chromatogr 499:177–196

    CAS  PubMed  Google Scholar 

  71. Lindner H, Sarg B, Meraner C, Helliger W (1996) Separation of acetylated core histones by hydrophilic-interaction liquid chromatography. J Chromatogr A 743(1):137–144

    CAS  PubMed  Google Scholar 

  72. Mizzen CA, Alpert AJ, Levesque L, Kruck TP, McLachlan DR (2000) Resolution of allelic and non-allelic variants of histone H1 by cation-exchange-hydrophilic-interaction chromatography. J Chromatogr B Biomed Sci Appl 744(1):33–46

    CAS  PubMed  Google Scholar 

  73. Plazas-Mayorca MD, Young NL, Garcia BA (2008) Identification of differentially expressed histone codes using HILIC chromatography and mass spectrometry. Am Biotechnol Lab 27(2):10–12

    Google Scholar 

  74. Young NL, Plazas-Mayorca MD, Garcia BA (2008) A method to separate and characterize modified forms of histones using HILIC chromatography and electron transfer dissociation-mass spectrometry. Am Biotechnol Lab 27(1):23–25

    Google Scholar 

  75. Sarg B, Helliger W, Talasz H, Forg B, Lindner HH (2006) Histone H1 phosphorylation occurs site-specifically during interphase and mitosis: identification of a novel phosphorylation site on histone H1. J Biol Chem 281(10):6573–6580

    CAS  PubMed  Google Scholar 

  76. Pesavento JJ, Mizzen CA, Kelleher NL (2006) Quantitative analysis of modified proteins and their positional isomers by tandem mass spectrometry: human histone H4. Anal Chem 78(13):4271–4280

    CAS  PubMed  Google Scholar 

  77. Taverna SD, Ueberheide BM, Liu Y, Tackett AJ, Diaz RL, Shabanowitz J, Chait BT, Hunt DF, Allis CD (2007) Long-distance combinatorial linkage between methylation and acetylation on histone H3 N termini. Proc Natl Acad Sci USA 104(7):2086–2091

    CAS  PubMed  Google Scholar 

  78. Young NL, DiMaggio PA, Plazas-Mayorca MD, Baliban RC, Floudas CA, Garcia BA (2009) High throughput characterization of combinatorial histone codes. Mol Cell Proteomics 8(10):2266–2284

    CAS  PubMed  Google Scholar 

  79. Zubarev RA, Kelleher NL, McLafferty FW (1998) Electron capture dissociation of multiply charged protein cations. A nonergodic process. J Am Chem Soc 120(13):3265–3266

    CAS  Google Scholar 

  80. Syka JE, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF (2004) Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci USA 101(26):9528–9533

    CAS  PubMed  Google Scholar 

  81. Zhang K, Tang H, Huang L, Blankenship JW, Jones PR, Xiang F, Yau PM, Burlingame AL (2002) Identification of acetylation and methylation sites of histone H3 from chicken erythrocytes by high-accuracy matrix-assisted laser desorption ionization-time-of-flight, matrix-assisted laser desorption ionization-postsource decay, and nanoelectrospray ionization tandem mass spectrometry. Anal Biochem 306(2):259–269

    CAS  PubMed  Google Scholar 

  82. Zhang K, Yau PM, Chandrasekhar B, New R, Kondrat R, Imai BS, Bradbury ME (2004) Differentiation between peptides containing acetylated or tri-methylated lysines by mass spectrometry: an application for determining lysine 9 acetylation and methylation of histone H3. Proteomics 4(1):1–10

    CAS  PubMed  Google Scholar 

  83. Garcia BA, Joshi S, Thomas CE, Chitta RK, Diaz RL, Busby SA, Andrews PC, Ogorzalek Loo RR, Shabanowitz J, Kelleher NL, Mizzen CA, Allis CD, Hunt DF (2006) Comprehensive phosphoprotein analysis of linker histone H1 from Tetrahymena thermophila. Mol Cell Proteomics 5(9):1593–1609

    CAS  PubMed  Google Scholar 

  84. Pesavento JJ, Bullock CR, LeDuc RD, Mizzen CA, Kelleher NL (2008) Combinatorial modification of human histone H4 quantitated by two-dimensional liquid chromatography coupled with top down mass spectrometry. J Biol Chem 283(22):14927–14937

    CAS  PubMed  Google Scholar 

  85. Medzihradszky KF, Zhang X, Chalkley RJ, Guan S, McFarland MA, Chalmers MJ, Marshall AG, Diaz RL, Allis CD, Burlingame AL (2004) Characterization of Tetrahymena histone H2B variants and posttranslational populations by electron capture dissociation (ECD) Fourier transform ion cyclotron mass spectrometry (FT-ICR MS). Mol Cell Proteomics 3(9):872–886

    CAS  PubMed  Google Scholar 

  86. Siuti N, Roth MJ, Mizzen CA, Kelleher NL, Pesavento JJ (2006) Gene-specific characterization of human histone H2B by electron capture dissociation. J Proteome Res 5(2):233–239

    CAS  PubMed  Google Scholar 

  87. Boyne MT 2nd, Pesavento JJ, Mizzen CA, Kelleher NL (2006) Precise characterization of human histones in the H2A gene family by top down mass spectrometry. J Proteome Res 5(2):248–253

    CAS  PubMed  Google Scholar 

  88. Zhang L, Freitas MA (2004) Comparison of peptide mass mapping and electron capture dissociation as assays for histone posttranslational modifications. Int J Mass Spectr 234(1–3):213–225

    CAS  Google Scholar 

  89. Thomas CE, Kelleher NL, Mizzen CA (2006) Mass spectrometric characterization of human histone H3: a bird’s eye view. J Proteome Res 5(2):240–247

    CAS  PubMed  Google Scholar 

  90. Parks BA, Jiang L, Thomas PM, Wenger CD, Roth MJ, Boyne MT 2nd, Burke PV, Kwast KE, Kelleher NL (2007) Top-down proteomics on a chromatographic time scale using linear ion trap Fourier transform hybrid mass spectrometers. Anal Chem 79(21):7984–7991

    CAS  PubMed  Google Scholar 

  91. Li M, Jiang L, Kelleher NL (2009) Global histone profiling by LC–FTMS after inhibition and knockdown of deacetylases in human cells. J Chromatogr B Analyt Technol Biomed Life Sci 877(30):3885–3892

    CAS  PubMed  Google Scholar 

  92. Pesavento JJ, Kim YB, Taylor GK, Kelleher NL (2004) Shotgun annotation of histone modifications: a new approach for streamlined characterization of proteins by top down mass spectrometry. J Am Chem Soc 126(11):3386–3387

    CAS  PubMed  Google Scholar 

  93. Phanstiel D, Brumbaugh J, Berggren WT, Conard K, Feng X, Levenstein ME, McAlister GC, Thomson JA, Coon JJ (2008) Mass spectrometry identifies and quantifies 74 unique histone H4 isoforms in differentiating human embryonic stem cells. Proc Natl Acad Sci USA 105(11):4093–4098

    CAS  PubMed  Google Scholar 

  94. Nicklay JJ, Shechter D, Chitta RK, Garcia BA, Shabanowitz J, Allis CD, Hunt DF (2009) Analysis of histones in Xenopus laevis. II. Mass spectrometry reveals an index of cell type-specific modifications on H3 and H4. J Biol Chem 284(2):1075–1085

    CAS  PubMed  Google Scholar 

  95. Hansen BT, Davey SW, Ham AJ, Liebler DC (2005) P-Mod: an algorithm and software to map modifications to peptide sequences using tandem MS data. J Proteome Res 4(2):358–368

    CAS  PubMed  Google Scholar 

  96. Tanner S, Pevzner PA, Bafna V (2006) Unrestrictive identification of post-translational modifications through peptide mass spectrometry. Nat Protoc 1(1):67–72

    CAS  PubMed  Google Scholar 

  97. Liu C, Yan B, Song Y, Xu Y, Cai L (2006) Peptide sequence tag-based blind identification of post-translational modifications with point process model. Bioinformatics 22(14):e307–e313

    CAS  PubMed  Google Scholar 

  98. Havilio M, Wool A (2007) Large-scale unrestricted identification of post-translation modifications using tandem mass spectrometry. Anal Chem 79(4):1362–1368

    CAS  PubMed  Google Scholar 

  99. Baumgartner C, Rejtar T, Kullolli M, Akella LM, Karger BL (2008) SeMoP: a new computational strategy for the unrestricted search for modified peptides using LC–MS/MS data. J Proteome Res 7(9):4199–4208

    CAS  PubMed  Google Scholar 

  100. Chen Y, Chen W, Cobb MH, Zhao Y (2009) PTMap—a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci USA 106(3):761–766

    CAS  PubMed  Google Scholar 

  101. Guan S, Burlingame AL (2010) Data processing algorithms for analysis of high resolution MSMS spectra of peptides with complex patterns of posttranslational modifications. Mol Cell Proteomics 9(5):804–810

    CAS  PubMed  Google Scholar 

  102. DiMaggio PA Jr, Young NL, Baliban RC, Garcia BA, Floudas CA (2009) A mixed integer linear optimization framework for the identification and quantification of targeted post-translational modifications of highly modified proteins using multiplexed electron transfer dissociation tandem mass spectrometry. Mol Cell Proteomics 8(11):2527–2543

    CAS  PubMed  Google Scholar 

  103. Loyola A, Bonaldi T, Roche D, Imhof A, Almouzni G (2006) PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. Mol Cell 24(2):309–316

    CAS  PubMed  Google Scholar 

  104. Dejardin J, Kingston RE (2009) Purification of proteins associated with specific genomic loci. Cell 136(1):175–186

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Princeton University, an NSF Early Faculty CAREER award, NSF grant (CBET-0941143) and a NJCCR SEED grant to B.A.G.; N.L.Y. and P.A.D. also gratefully acknowledge funding from NIH F32 NRSA postdoctoral fellowships.

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, 415 Schultz Laboratory, Princeton, NJ, 08544, USA

    Nicolas L. Young, Peter A. DiMaggio & Benjamin A. Garcia

  2. Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA

    Benjamin A. Garcia

Authors
  1. Nicolas L. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter A. DiMaggio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benjamin A. Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benjamin A. Garcia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Young, N.L., DiMaggio, P.A. & Garcia, B.A. The significance, development and progress of high-throughput combinatorial histone code analysis. Cell. Mol. Life Sci. 67, 3983–4000 (2010). https://doi.org/10.1007/s00018-010-0475-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-010-0475-7

Keywords

Search

Navigation