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Review

The Contribution of Mass Spectrometry-Based Proteomics to Understanding Epigenetics

, &
Pages 429-445 | Received 16 Oct 2015, Accepted 11 Nov 2015, Published online: 25 Nov 2015

References

  • Jenuwein T , AllisCD . Translating the histone code . Science293 ( 5532 ), 1074 – 1080 ( 2001 ).
  • Bannister AJ , KouzaridesT . Regulation of chromatin by histone modifications . Cell Res.21 ( 3 ), 381 – 395 ( 2011 ).
  • Yuan G , ZhuB . Histone variants and epigenetic inheritance . Biochim. Biophys. Acta1819 ( 3–4 ), 222 – 229 ( 2012 ).
  • Skene PJ , HenikoffS . Histone variants in pluripotency and disease . Development140 ( 12 ), 2513 – 2524 ( 2013 ).
  • Huang H , LinS , GarciaBA , ZhaoY . Quantitative proteomic analysis of histone modifications . Chem. Rev.115 ( 6 ), 2376 – 2418 ( 2015 ).
  • Soldi M , CuomoA , BremangM , BonaldiT . Mass spectrometry-based proteomics for the analysis of chromatin structure and dynamics . Int. J. Mol. Sci.14 ( 3 ), 5402 – 5431 ( 2013 ).
  • Bonaldi T , ImhofA , RegulaJT . A combination of different mass spectroscopic techniques for the analysis of dynamic changes of histone modifications . Proteomics4 ( 5 ), 1382 – 1396 ( 2004 ).
  • Smith CM , HaimbergerZW , JohnsonCOet al. Heritable chromatin structure: mapping “memory” in histones H3 and H4 . Proc. Natl Acad. Sci. USA99 ( Suppl. 4 ), 16454 – 16461 ( 2002 ).
  • Garcia BA , MollahS , UeberheideBMet al. Chemical derivatization of histones for facilitated analysis by mass spectrometry . Nat. Protoc.2 ( 4 ), 933 – 938 ( 2007 ).
  • Bonaldi T , RegulaJT , ImhofA . The use of mass spectrometry for the analysis of histone modifications . Methods Enzymol.377 , 111 – 130 ( 2004 ).
  • Sidoli S , YuanZF , LinSet al. Drawbacks in the use of unconventional hydrophobic anhydrides for histone derivatization in bottom–up proteomics PTM analysis . Proteomics15 ( 9 ), 1459 – 1469 ( 2015 ).
  • Soldi M , CuomoA , BonaldiT . Improved bottom–up strategy to efficiently separate hypermodified histone peptides through ultra-HPLC separation on a bench top Orbitrap instrument . Proteomics14 ( 19 ), 2212 – 2125 ( 2014 ).
  • Maile TM , Izrael-TomasevicA , CheungTet al. Mass spectrometric quantification of histone post-translational modifications by a hybrid chemical labeling method . Mol. Cell. Proteomics14 ( 4 ), 1148 – 1158 ( 2015 ).
  • Thomas CE , KelleherNL , MizzenCA . Mass spectrometric characterization of human histone H3: a bird’s eye view . J. Proteome Res.5 ( 2 ), 240 – 247 ( 2006 ).
  • Young NL , DimaggioPA , Plazas-MayorcaMD , BalibanRC , FloudasCA , GarciaBA . High throughput characterization of combinatorial histone codes . Mol. Cell. Proteomics8 ( 10 ), 2266 – 2284 ( 2009 ).
  • Taverna SD , UeberheideBM , LiuYet al. Long-distance combinatorial linkage between methylation and acetylation on histone H3 N termini . Proc. Natl Acad. Sci. USA104 ( 7 ), 2086 – 2091 ( 2007 ).
  • Nicklay JJ , ShechterD , ChittaRKet al. 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 ( 2009 ).
  • Plazas-Mayorca MD , BloomJS , ZeisslerUet al. Quantitative proteomics reveals direct and indirect alterations in the histone code following methyltransferase knockdown . Mol. Biosyst.6 ( 9 ), 1719 – 1729 ( 2010 ).
  • Bonet-Costa C , VilasecaM , DiemaCet al. Combined bottom–up and top–down mass spectrometry analyses of the pattern of post-translational modifications of Drosophila melanogaster linker histone H1 . J. Proteomics75 ( 13 ), 4124 – 4138 ( 2012 ).
  • Zhao Y , GarciaBA . Comprehensive catalog of currently documented histone modifications . Cold Spring Harb. Perspect. Biol.7 ( 9 ), a025064 ( 2015 ).
  • Strahl BD , BriggsSD , BrameCJet al. Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1 . Curr. Biol.11 ( 12 ), 996 – 1000 ( 2001 ).
  • Casadio F , LuX , PollockSBet al. H3R42me2a is a histone modification with positive transcriptional effects . Proc. Natl. Acad. Sci. USA110 ( 37 ), 14894 – 14899 ( 2013 ).
  • Wisniewski JR , ZougmanA , MannM . Nepsilon-formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function . Nucleic Acids Res.36 ( 2 ), 570 – 577 ( 2008 ).
  • Sakabe K , WangZ , HartGW . Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code . Proc. Natl. Acad. Sci. USA107 ( 46 ), 19915 – 19920 ( 2010 ).
  • Zhang K , ChenY , ZhangZ , ZhaoY . Identification and verification of lysine propionylation and butyrylation in yeast core histones using PTMap software . J. Proteome Res.8 ( 2 ), 900 – 906 ( 2009 ).
  • Chen Y , SprungR , TangYet al. Lysine propionylation and butyrylation are novel post-translational modifications in histones . Mol. Cell. Proteomics6 ( 5 ), 812 – 819 ( 2007 .
  • Xie Z , DaiJ , DaiLet al. Lysine succinylation and lysine malonylation in histones . Mol. Cell. Proteomics11 ( 5 ), 100 – 107 ( 2012 ).
  • Pesavento JJ , MizzenCA , KelleherNL . Quantitative analysis of modified proteins and their positional isomers by tandem mass spectrometry: human histone H4 . Anal. Chem.78 ( 13 ), 4271 – 4280 ( 2006 ).
  • Garcia BA , PesaventoJJ , MizzenCA , KelleherNL . Pervasive combinatorial modification of histone H3 in human cells . Nat. Methods4 ( 6 ), 487 – 489 ( 2007 ).
  • Fraga MF , BallestarE , Villar-GareaAet al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer . Nat. Genet.37 ( 4 ), 391 – 400 ( 2005 ).
  • Leroy G , DimaggioPA , ChanEYet al. A quantitative atlas of histone modification signatures from human cancer cells . Epigenetics Chromatin6 ( 1 ), 20 ( 2013 ).
  • Sundar IK , NevidMZ , FriedmanAE , RahmanI . Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer . J. Proteome Res.13 ( 2 ), 982 – 996 ( 2014 ).
  • Zhang K , LiL , ZhuMet al. Comparative analysis of histone H3 and H4 post-translational modifications of esophageal squamous cell carcinoma with different invasive capabilities . J. Proteomics112 , 180 – 189 ( 2014 ).
  • Voigt P , LeroyG , DruryWJ3rdet al. Asymmetrically modified nucleosomes . Cell151 ( 1 ), 181 – 193 ( 2012 ).
  • Ong SE , BlagoevB , KratchmarovaIet al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics . Mol. Cell. Proteomics1 ( 5 ), 376 – 386 ( 2002 ).
  • Pesavento JJ , YangH , KelleherNL , MizzenCA . Certain and progressive methylation of histone H4 at lysine 20 during the cell cycle . Mol. Cell. Biol.28 ( 1 ), 468 – 486 ( 2008 ).
  • Bonenfant D , TowbinH , CoulotM , SchindlerP , MuellerDR , Van OostrumJ . Analysis of dynamic changes in post-translational modifications of human histones during cell cycle by mass spectrometry . Mol. Cell. Proteomics6 ( 11 ), 1917 – 1932 ( 2007 ).
  • Mews P , ZeeBM , LiuS , DonahueG , GarciaBA , BergerSL . Histone methylation has dynamics distinct from those of histone acetylation in cell cycle reentry from quiescence . Mol. Cell. Biol.34 ( 21 ), 3968 – 3980 ( 2014 ).
  • Scharf AN , MeierK , SeitzV , KremmerE , BrehmA , ImhofA . Monomethylation of lysine 20 on histone H4 facilitates chromatin maturation . Mol. Cell. Biol.29 ( 1 ), 57 – 67 ( 2009 ).
  • Guan X , RastogiN , ParthunMR , FreitasMA . Discovery of histone modification crosstalk networks by stable isotope labeling of amino acids in cell culture mass spectrometry (SILAC MS) . Mol. Cell. Proteomics12 ( 8 ), 2048 – 2059 ( 2013 ).
  • Cuomo A , MorettiS , MinucciS , BonaldiT . SILAC-based proteomic analysis to dissect the “histone modification signature” of human breast cancer cells . Amino Acids41 ( 2 ), 387 – 399 ( 2011 ).
  • Jaffe JD , WangY , ChanHMet al. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia . Nat. Genet.45 ( 11 ), 1386 – 1391 ( 2013 ).
  • Noberini R , UggettiA , PruneriG , MinucciS , BonaldiT . Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples . Mol. Cell Proteomics doi:10.1074/mcp.M115.054510 ( 2015 ) ( Epub ahead of print ).
  • Geiger T , CoxJ , OstasiewiczP , WisniewskiJR , MannM . Super-SILAC mix for quantitative proteomics of human tumor tissue . Nat. Methods7 ( 5 ), 383 – 385 ( 2010 ).
  • Ong SE , MittlerG , MannM . Identifying and quantifying in vivo methylation sites by heavy methyl SILAC . Nat. Methods1 ( 2 ), 119 – 126 ( 2004 ).
  • Fodor BD , KubicekS , YonezawaMet al. Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells . Genes Dev.20 ( 12 ), 1557 – 1562 ( 2006 ).
  • Zee BM , LevinRS , XuB , LeroyG , WingreenNS , GarciaBA . In vivo residue-specific histone methylation dynamics . J. Biol. Chem.285 ( 5 ), 3341 – 3350 ( 2010 ).
  • Sweet SM , LiM , ThomasPM , DurbinKR , KelleherNL . Kinetics of re-establishing H3K79 methylation marks in global human chromatin . J. Biol. Chem.285 ( 43 ), 32778 – 32786 ( 2010 ).
  • Zee BM , LevinRS , DimaggioPA , GarciaBA . Global turnover of histone post-translational modifications and variants in human cells . Epigenetics Chromatin3 ( 1 ), 22 ( 2010 ).
  • Plazas-Mayorca MD , ZeeBM , YoungNLet al. One-pot shotgun quantitative mass spectrometry characterization of histones . J. Proteome Res.8 ( 11 ), 5367 – 5374 ( 2009 ).
  • Weinert BT , LesmantaviciusV , MoustafaTet al. Acetylation dynamics and stoichiometry in Saccharomyces cerevisiae . Mol. Syst. Biol.10 , 716 ( 2014 ).
  • Picotti P , AebersoldR . Selected reaction monitoring-based proteomics: workflows, potential, pitfalls and future directions . Nat. Methods9 ( 6 ), 555 – 566 ( 2012 ).
  • Darwanto A , CurtisMP , SchragMet al. A modified “cross-talk” between histone H2B Lys-120 ubiquitination and H3 Lys-79 methylation . J. Biol. Chem.285 ( 28 ), 21868 – 21876 ( 2010 ).
  • Gao J , LiaoR , YuYet al. Absolute quantification of histone PTM marks by MRM-based LC-MS/MS . Anal. Chem.86 ( 19 ), 9679 – 9686 ( 2014 ).
  • Lin S , WeinS , Gonzales-CopeMet al. Stable-isotope-labeled histone peptide library for histone post-translational modification and variant quantification by mass spectrometry . Mol. Cell. Proteomics13 ( 9 ), 2450 – 2466 ( 2014 ).
  • Tang H , FangH , YinE , BrasierAR , SowersLC , ZhangK . Multiplexed parallel reaction monitoring targeting histone modifications on the QExactive mass spectrometer . Anal. Chem.86 ( 11 ), 5526 – 5534 ( 2014 ).
  • Schwartzentruber J , KorshunovA , LiuXYet al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma . Nature482 ( 7384 ), 226 – 231 ( 2012 ).
  • Jiang L , SmithJN , AndersonSL , MaP , MizzenCA , KelleherNL . 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 ( 2007 ).
  • Chen Y , HooverME , DangXet al. Quantitative mass spectrometry reveals that intact histone H1 phosphorylations are variant specific and exhibit single molecule hierarchical dependence . Mol. Cell. Proteomics doi:10.1074/mcp.M114.046441 ( 2015 ) ( Epub ahead of print ).
  • Siuti N , RothMJ , MizzenCA , KelleherNL , PesaventoJJ . Gene-specific characterization of human histone H2B by electron capture dissociation . J. Proteome Res.5 ( 2 ), 233 – 239 ( 2006 ).
  • Boyne MT 2nd , PesaventoJJ , MizzenCA , KelleherNL . Precise characterization of human histones in the H2A gene family by top down mass spectrometry . J. Proteome Res.5 ( 2 ), 248 – 253 ( 2006 ).
  • Tvardovskiy A , WrzesinskiK , SidoliS , FeySJ , Rogowska-WrzesinskaA , JensenON . Top–down and middle–down protein analysis reveals that intact and clipped human histones differ in post-translational modification patterns . Mol. Cell. Proteomics doi:10.1074/mcp.M115.048975 ( 2015 ) ( Epub ahead of print ).
  • Loyola A , BonaldiT , RocheD , ImhofA , AlmouzniG . PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state . Mol. Cell24 ( 2 ), 309 – 316 ( 2006 ).
  • Imhof A , BonaldiT . “Chromatomics” the analysis of the chromatome . Mol. Biosyst.1 ( 2 ), 112 – 116 ( 2005 ).
  • Soldi M , BremangM , BonaldiT . Biochemical systems approaches for the analysis of histone modification readout . Biochim. Biophys. Acta1839 ( 8 ), 657 – 668 ( 2014 ).
  • Shiio Y , EisenmanRN , YiEC , DonohoeS , GoodlettDR , AebersoldR . Quantitative proteomic analysis of chromatin-associated factors . J. Am. Soc. Mass Spectrom.14 ( 7 ), 696 – 703 ( 2003 ).
  • Kubota T , HiragaS , YamadaK , LamondAI , DonaldsonAD . Quantitative proteomic analysis of chromatin reveals that Ctf18 acts in the DNA replication checkpoint . Mol. Cell. Proteomics10 ( 7 ), M110 005561 ( 2011 ).
  • Kim DR , GidvaniRD , IngallsBP , DunckerBP , McconkeyBJ . Differential chromatin proteomics of the MMS-induced DNA damage response in yeast . Proteome Sci.9 , 62 ( 2011 ).
  • Khoudoli GA , GillespiePJ , StewartG , AndersenJS , SwedlowJR , BlowJJ . Temporal profiling of the chromatin proteome reveals system-wide responses to replication inhibition . Curr. Biol.18 ( 11 ), 838 – 843 ( 2008 ).
  • Chou DM , AdamsonB , DephoureNEet al. A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage . Proc. Natl. Acad. Sci. USA107 ( 43 ), 18475 – 18480 ( 2010 ).
  • Franklin S , ChenH , Mitchell-JordanS , RenS , WangY , VondriskaTM . Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth . Mol. Cell. Proteomics11 ( 6 ), M111 014258 ( 2012 ).
  • Alajem A , BiranA , HarikumarAet al. Differential association of chromatin proteins identifies BAF60a/SMARCD1 as a regulator of embryonic stem cell differentiation . Cell Rep.10 ( 12 ), 2019 – 2031 ( 2015 ).
  • Kustatscher G , HegaratN , WillsKLet al. Proteomics of a fuzzy organelle: interphase chromatin . EMBO J.33 ( 6 ), 648 – 664 ( 2014 ).
  • Kustatscher G , WillsKL , FurlanC , RappsilberJ . Chromatin enrichment for proteomics . Nat. Protoc.9 ( 9 ), 2090 – 2099 ( 2014 ).
  • Han Y , YuanZF , MoldenRC , GarciaBA . Monitoring cellular phosphorylation signaling pathways into chromatin and down to the gene level . Mol. Cell. Proteomics doi:10.1074/mcp.M115.053421 ( 2015 ) ( Epub ahead of print ).
  • Wysocka J , SwigutT , MilneTAet al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development . Cell121 ( 6 ), 859 – 872 ( 2005 ).
  • Wysocka J , SwigutT , XiaoHet al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling . Nature442 ( 7098 ), 86 – 90 ( 2006 ).
  • Vermeulen M , EberlHC , MatareseFet al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers . Cell142 ( 6 ), 967 – 980 ( 2010 ).
  • Vermeulen M , MulderKW , DenissovSet al. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4 . Cell131 ( 1 ), 58 – 69 ( 2007 ).
  • Poser I , SarovM , HutchinsJRet al. BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals . Nat. Methods5 ( 5 ), 409 – 415 ( 2008 ).
  • Li X , FoleyEA , MolloyKR , LiY , ChaitBT , KapoorTM . Quantitative chemical proteomics approach to identify post-translational modification-mediated protein-protein interactions . J. Am. Chem. Soc.134 ( 4 ), 1982 – 1985 ( 2012 ).
  • Bartke T , VermeulenM , XhemalceB , RobsonSC , MannM , KouzaridesT . Nucleosome-interacting proteins regulated by DNA and histone methylation . Cell143 ( 3 ), 470 – 484 ( 2010 ).
  • Nikolov M , StutzerA , MoschKet al. Chromatin affinity purification and quantitative mass spectrometry defining the interactome of histone modification patterns . Mol. Cell. Proteomics10 ( 11 ), M110 005371 ( 2011 ).
  • Shema-Yaacoby E , NikolovM , Haj-YahyaMet al. Systematic identification of proteins binding to chromatin-embedded ubiquitylated H2B reveals recruitment of SWI/SNF to regulate transcription . Cell Rep.4 ( 3 ), 601 – 608 ( 2013 ).
  • Mittler G , ButterF , MannM . A SILAC-based DNA protein interaction screen that identifies candidate binding proteins to functional DNA elements . Genome Res.19 ( 2 ), 284 – 293 ( 2009 ).
  • Spruijt CG , GnerlichF , SmitsAHet al. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives . Cell152 ( 5 ), 1146 – 1159 ( 2013 ).
  • Lambert JP , MitchellL , RudnerA , BaetzK , FigeysD . A novel proteomics approach for the discovery of chromatin-associated protein networks . Mol. Cell. Proteomics8 ( 4 ), 870 – 882 ( 2009 ).
  • Soldi M , BonaldiT . The proteomic investigation of chromatin functional domains reveals novel synergisms among distinct heterochromatin components . Mol. Cell. Proteomics12 ( 3 ), 764 – 780 ( 2013 ).
  • Won KJ , ChoiI , LeroyGet al. Proteogenomics analysis reveals specific genomic orientations of distal regulatory regions composed by non-canonical histone variants . Epigenetics Chromatin8 , 13 ( 2015 ).
  • Ji X , DadonDB , AbrahamBJet al. Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions . Proc. Natl Acad. Sci. USA112 ( 12 ), 3841 – 3846 ( 2015 ).
  • Mohammed H , D’SantosC , SerandourAAet al. Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor . Cell Rep.3 ( 2 ), 342 – 349 ( 2013 ).
  • Mohammed H , RussellIA , StarkRet al. Progesterone receptor modulates ERalpha action in breast cancer . Nature523 ( 7560 ), 313 – 317 ( 2015 ).
  • Wang CI , AlekseyenkoAA , LeroyGet al. Chromatin proteins captured by ChIP-mass spectrometry are linked to dosage compensation in Drosophila . Nat. Struct. Mol. Biol.20 ( 2 ), 202 – 209 ( 2013 ).
  • Sirbu BM , CouchFB , CortezD . Monitoring the spatiotemporal dynamics of proteins at replication forks and in assembled chromatin using isolation of proteins on nascent DNA . Nat. Protoc.7 ( 3 ), 594 – 605 ( 2012 ).
  • Alabert C , Bukowski-WillsJC , LeeSBet al. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components . Nat. Cell Biol.16 ( 3 ), 281 – 293 ( 2014 ).
  • Alabert C , BarthTK , Reveron-GomezNet al. Two distinct modes for propagation of histone PTMs across the cell cycle . Genes Dev.29 ( 6 ), 585 – 590 ( 2015 ).
  • Antao JM , MasonJM , DejardinJ , KingstonRE . Protein landscape at Drosophila melanogaster telomere-associated sequence repeats . Mol. Cell. Biol.32 ( 12 ), 2170 – 2182 ( 2012 ).
  • Dejardin J , KingstonRE . Purification of proteins associated with specific genomic loci . Cell136 ( 1 ), 175 – 186 ( 2009 ).
  • Unnikrishnan A , GafkenPR , TsukiyamaT . Dynamic changes in histone acetylation regulate origins of DNA replication . Nat. Struct. Mol. Biol.17 ( 4 ), 430 – 437 ( 2010 ).
  • Byrum SD , RamanA , TavernaSD , TackettAJ . ChAP-MS: a method for identification of proteins and histone posttranslational modifications at a single genomic locus . Cell Rep.2 ( 1 ), 198 – 205 ( 2012 ).
  • Byrum SD , TavernaSD , TackettAJ . Purification of a specific native genomic locus for proteomic analysis . Nucleic Acids Res.41 ( 20 ), e195 ( 2013 ).
  • Qi LS , LarsonMH , GilbertLAet al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression . Cell152 ( 5 ), 1173 – 1183 ( 2013 ).
  • Waldrip ZJ , ByrumSD , StoreyAJet al. A CRISPR-based approach for proteomic analysis of a single genomic locus . Epigenetics9 ( 9 ), 1207 – 1211 ( 2014 ).
  • Fujita T , FujiiH . Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR . Biochem. Biophys. Res. Commun.439 ( 1 ), 132 – 136 ( 2013 ).
  • Fujita T , AsanoY , OhtsukaJet al. Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) . Sci. Rep.3 , 3171 ( 2013 ).
  • Torrente MP , ZeeBM , YoungNLet al. Proteomic interrogation of human chromatin . PLoS ONE6 ( 9 ), e24747 ( 2011 ).
  • Chen M , ManleyJL . Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches . Nat. Rev. Mol. Cell Biol.10 ( 11 ), 741 – 754 ( 2009 ).
  • Licatalosi DD , DarnellRB . RNA processing and its regulation: global insights into biological networks . Nat. Rev. Genet.11 ( 1 ), 75 – 87 ( 2010 ).
  • McHugh CA , RussellP , GuttmanM . Methods for comprehensive experimental identification of RNA-protein interactions . Genome Biol.15 ( 1 ), 203 ( 2014 ).
  • Baltz AG , MunschauerM , SchwanhausserBet al. The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts . Mol. Cell46 ( 5 ), 674 – 690 ( 2012 ).
  • Castello A , FischerB , EichelbaumKet al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins . Cell149 ( 6 ), 1393 – 1406 ( 2012 ).
  • Klass DM , ScheibeM , ButterF , HoganGJ , MannM , BrownPO . Quantitative proteomic analysis reveals concurrent RNA-protein interactions and identifies new RNA-binding proteins in Saccharomyces cerevisiae . Genome Res.23 ( 6 ), 1028 – 1038 ( 2013 ).
  • Kramer K , SachsenbergT , BeckmannBMet al. Photo-cross-linking and high-resolution mass spectrometry for assignment of RNA-binding sites in RNA-binding proteins . Nat. Methods11 ( 10 ), 1064 – 1070 ( 2014 ).
  • Yang Y , WenL , ZhuH . Unveiling the hidden function of long non-coding RNA by identifying its major partner-protein . Cell Biosci.5 , 59 ( 2015 ).
  • Rinn JL , ChangHY . Genome regulation by long noncoding RNAs . Annu. Rev. Biochem.81 , 145 – 166 ( 2012 ).
  • Chu C , ZhangQC , Da RochaSTet al. Systematic discovery of Xist RNA binding proteins . Cell161 ( 2 ), 404 – 416 ( 2015 ).
  • West JA , DavisCP , SunwooHet al. The long noncoding RNAs NEAT1 and MALAT1 bind active chromatin sites . Mol. Cell55 ( 5 ), 791 – 802 ( 2014 ).
  • Mchugh CA , ChenCK , ChowAet al. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3 . Nature521 ( 7551 ), 232 – 236 ( 2015 ).
  • Portela A , EstellerM . Epigenetic modifications and human disease . Nat. Biotechnol.28 ( 10 ), 1057 – 1068 ( 2010 ).
  • Seligson DB , HorvathS , McBrianMAet al. Global levels of histone modifications predict prognosis in different cancers . Am. J. Pathol.174 ( 5 ), 1619 – 1628 ( 2009 ).
  • Seligson DB , HorvathS , ShiTet al. Global histone modification patterns predict risk of prostate cancer recurrence . Nature435 ( 7046 ), 1262 – 1266 ( 2005 ).
  • Chi P , AllisCD , WangGG . Covalent histone modifications – miswritten, misinterpreted and mis-erased in human cancers . Nat. Rev. Cancer10 ( 7 ), 457 – 469 ( 2010 ).
  • Nebbioso A , CarafaV , BenedettiR , AltucciL . Trials with ‘epigenetic’ drugs: an update . Mol. Oncol.6 ( 6 ), 657 – 682 ( 2012 ).
  • Heyn H , EstellerM . DNA methylation profiling in the clinic: applications and challenges . Nat. Rev. Genet.13 ( 10 ), 679 – 692 ( 2012 ).
  • Garcia BA , BusbySA , ShabanowitzJ , HuntDF , MishraN . Resetting the epigenetic histone code in the MRL-lpr/lpr mouse model of lupus by histone deacetylase inhibition . J. Proteome Res.4 ( 6 ), 2032 – 2042 ( 2005 ).
  • Harshman SW , HooverME , HuangCet al. Histone H1 phosphorylation in breast cancer . J. Proteome Res.13 ( 5 ), 2453 – 2467 ( 2014 ).
  • Zheng Y , FornelliL , ComptonPDet al. Unabridged analysis of human histone H3 by differential top–down mass spectrometry reveals hypermethylated proteoforms from MMSET/NSD2 overexpression . Mol. Cell. Proteomics doi:10.1074/mcp.M115.053819 ( 2015 ) ( Epub ahead of print ).
  • Xu G , WangJ , WuZet al. SAHA regulates histone acetylation, butyrylation, and protein expression in neuroblastoma . J. Proteome Res.13 ( 10 ), 4211 – 4219 ( 2014 ).
  • Cazares LH , TroyerDA , WangB , DrakeRR , SemmesOJ . MALDI tissue imaging: from biomarker discovery to clinical applications . Anal. Bioanal. Chem.401 ( 1 ), 17 – 27 ( 2011 ).
  • Munteanu B , MeyerB , Von ReitzensteinCet al. Label-free in situ monitoring of histone deacetylase drug target engagement by matrix-assisted laser desorption ionization-mass spectrometry biotyping and imaging . Anal. Chem.86 ( 10 ), 4642 – 4647 ( 2014 ).
  • Pote N , AlexandrovT , Le FaouderJet al. Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers of microvascular invasion in hepatocellular carcinomas . Hepatology58 ( 3 ), 983 – 994 ( 2013 ).
  • Bantscheff M , ScholtenA , HeckAJ . Revealing promiscuous drug-target interactions by chemical proteomics . Drug Discov. Today14 ( 21–22 ), 1021 – 1029 ( 2009 ).
  • Rix U , Superti-FurgaG . Target profiling of small molecules by chemical proteomics . Nat. Chem. Biol.5 ( 9 ), 616 – 624 ( 2009 ).
  • Bantscheff M , HopfC , SavitskiMMet al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes . Nat. Biotechnol.29 ( 3 ), 255 – 265 ( 2011 ).
  • Salisbury CM , CravattBF . Activity-based probes for proteomic profiling of histone deacetylase complexes . Proc. Natl Acad. Sci. USA104 ( 4 ), 1171 – 1176 ( 2007 ).
  • Dawson MA , PrinjhaRK , DittmannAet al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia . Nature478 ( 7370 ), 529 – 533 ( 2011 ).
  • Chung CW , CosteH , WhiteJHet al. Discovery and characterization of small molecule inhibitors of the BET family bromodomains . J. Med. Chem.54 ( 11 ), 3827 – 3838 ( 2011 ).
  • Nicodeme E , JeffreyKL , SchaeferUet al. Suppression of inflammation by a synthetic histone mimic . Nature468 ( 7327 ), 1119 – 1123 ( 2010 ).
  • Huang SM , MishinaYM , LiuSet al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling . Nature461 ( 7264 ), 614 – 620 ( 2009 ).
  • Emami KH , NguyenC , MaHet al. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected] . Proc. Natl Acad. Sci. USA101 ( 34 ), 12682 – 12687 ( 2004 ).
  • Savitski MM , ReinhardFB , FrankenHet al. Tracking cancer drugs in living cells by thermal profiling of the proteome . Science346 ( 6205 ), 1255784 ( 2014 ).
  • Franken H , MathiesonT , ChildsDet al. Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry . Nat. Protoc.10 ( 10 ), 1567 – 1593 ( 2015 ).
  • Scholz C , WeinertBT , WagnerSAet al. Acetylation site specificities of lysine deacetylase inhibitors in human cells . Nat. Biotechnol.33 ( 4 ), 415 – 423 ( 2015 ).
  • Sidoli S , LinS , XiongLet al. Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH) Analysis for characterization and quantification of histone post-translational modifications . Mol. Cell. Proteomics14 ( 9 ), 2420 – 2428 ( 2015 ).
  • Fanelli M , AmatoriS , BarozziIet al. Pathology tissue-chromatin immunoprecipitation, coupled with high-throughput sequencing, allows the epigenetic profiling of patient samples . Proc. Natl Acad. Sci. USA107 ( 50 ), 21535 – 21540 ( 2010 ).
  • Amatori S , BallariniM , FaversaniAet al. PAT-ChIP coupled with laser microdissection allows the study of chromatin in selected cell populations from paraffin-embedded patient samples . Epigenet. Chromatin7 , 18 ( 2014 ).