1932

Abstract

The field of epigenetics has exploded over the last two decades, revealing an astonishing level of complexity in the way genetic information is stored and accessed in eukaryotes. This expansion of knowledge, which is very much ongoing, has been made possible by the availability of evermore sensitive and precise molecular tools. This review focuses on the increasingly important role that chemistry plays in this burgeoning field. In an effort to make these contributions more accessible to the nonspecialist, we group available chemical approaches into those that allow the covalent structure of the protein and DNA components of chromatin to be manipulated, those that allow the activity of myriad factors that act on chromatin to be controlled, and those that allow the covalent structure and folding of chromatin to be characterized. The application of these tools is illustrated through a series of case studies that highlight how the molecular precision afforded by chemistry is being used to establish causal biochemical relationships at the heart of epigenetic regulation.

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2021-06-20
2024-12-04
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Literature Cited

  1. 1. 
    Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. 1997. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:251–60
    [Google Scholar]
  2. 2. 
    Clapier CR, Iwasa J, Cairns BR, Peterson CL. 2017. Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat. Rev. Mol. Cell Biol. 18:407–22
    [Google Scholar]
  3. 3. 
    Woodcock CL, Ghosh RP. 2010. Chromatin higher-order structure and dynamics. Cold Spring Harb. Perspect. Biol. 2:a000596
    [Google Scholar]
  4. 4. 
    Huang H, Sabari BR, Garcia BA, Allis CD, Zhao Y. 2014. SnapShot: histone modifications. Cell 159:458–58.e1
    [Google Scholar]
  5. 5. 
    Jenuwein T, Allis CD. 2001. Translating the histone code. Science 293:1074–80
    [Google Scholar]
  6. 6. 
    Dawson MA, Kouzarides T. 2012. Cancer epigenetics: from mechanism to therapy. Cell 150:12–27
    [Google Scholar]
  7. 7. 
    Budhavarapu VN, Chavez M, Tyler JK. 2013. How is epigenetic information maintained through DNA replication?. Epigenet. Chromatin 6:32
    [Google Scholar]
  8. 8. 
    Allfrey VG, Littau VC, Mirsky AE 1963. On the role of histones in regulating ribonucleic acid synthesis in the cell nucleus. PNAS 49:414–21
    [Google Scholar]
  9. 9. 
    Huang R-C, Bonner J 1962. Histone, a suppressor of chromosomal RNA synthesis. PNAS 48:1216–22
    [Google Scholar]
  10. 10. 
    Allfrey VG, Faulkner R, Mirsky AE 1964. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. PNAS 51:786–94
    [Google Scholar]
  11. 11. 
    Krieger DE, Vidali G, Erickson BW, Allfrey VG, Merrifield RB. 1979. The synthesis of diacetylated histone H4-(1–37) for studies on the mechanism of histone deacetylation. Bioorg. Chem. 8:409–27
    [Google Scholar]
  12. 12. 
    Krieger DE, Levine R, Merrifield RB, Vidali G, Allfrey VG. 1974. Chemical studies of histone acetylation. J. Biol. Chem. 249:332–34
    [Google Scholar]
  13. 13. 
    Taunton J, Collins JL, Schreiber SL. 1996. Synthesis of natural and modified trapoxins, useful reagents for exploring histone deacetylase function. J. Am. Chem. Soc. 118:10412–22
    [Google Scholar]
  14. 14. 
    Taunton J, Hassig CA, Schreiber SL. 1996. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272:408–11
    [Google Scholar]
  15. 15. 
    Müller MM, Muir TW. 2015. Histones: at the crossroads of peptide and protein chemistry. Chem. Rev. 115:2296–349
    [Google Scholar]
  16. 16. 
    Fischle W, Schwarzer D. 2016. Probing chromatin-modifying enzymes with chemical tools. ACS Chem. Biol. 11:689–705
    [Google Scholar]
  17. 17. 
    Boichenko I, Fierz B. 2019. Chemical and biophysical methods to explore dynamic mechanisms of chromatin silencing. Curr. Opin. Chem. Biol. 51:1–10
    [Google Scholar]
  18. 18. 
    Booth MJ, Raiber E-A, Balasubramanian S. 2015. Chemical methods for decoding cytosine modifications in DNA. Chem. Rev. 115:2240–54
    [Google Scholar]
  19. 19. 
    Reuter JA, Spacek DV, Snyder MP. 2015. High-throughput sequencing technologies. Mol. Cell 58:586–97
    [Google Scholar]
  20. 20. 
    Thompson RE, Muir TW. 2020. Chemoenzymatic semisynthesis of proteins. Chem. Rev. 120:3051–126
    [Google Scholar]
  21. 21. 
    Debelouchina GT, Muir TW. 2017. A molecular engineering toolbox for the structural biologist. Q. Rev. Biophys. 50:e7
    [Google Scholar]
  22. 22. 
    Simon MD, Chu F, Racki LR, de la Cruz CC, Burlingame AL et al. 2007. The site-specific installation of methyl-lysine analogs into recombinant histones. Cell 128:1003–12
    [Google Scholar]
  23. 23. 
    Dadová J, Galan SR, Davis BG. 2018. Synthesis of modified proteins via functionalization of dehydroalanine. Curr. Opin. Chem. Biol. 46:71–81
    [Google Scholar]
  24. 24. 
    Lechner CC, Agashe ND, Fierz B. 2016. Traceless synthesis of asymmetrically modified bivalent nucleosomes. Angew. Chem. Int. Ed. 55:2903–6
    [Google Scholar]
  25. 25. 
    Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ et al. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–26
    [Google Scholar]
  26. 26. 
    Lang K, Chin JW. 2014. Cellular incorporation of unnatural amino acids and bioorthogonal labeling of proteins. Chem. Rev. 114:4764–806
    [Google Scholar]
  27. 27. 
    Nguyen DP, Alai MMG, Kapadnis PB, Neumann H, Chin JW. 2009. Genetically encoding Nε-methyl-l-lysine in recombinant histones. J. Am. Chem. Soc. 131:14194–95
    [Google Scholar]
  28. 28. 
    Neumann H, Peak-Chew SY, Chin JW 2008. Genetically encoding Nε-acetyllysine in recombinant proteins. Nat. Chem. Biol. 4:232–34
    [Google Scholar]
  29. 29. 
    Lee S, Oh S, Yang A, Kim J, Söll D et al. 2013. A facile strategy for selective incorporation of phosphoserine into histones. Angew. Chem. Int. Ed. 52:5771–75
    [Google Scholar]
  30. 30. 
    Gattner MJ, Vrabel M, Carell T. 2013. Synthesis of ε-N-propionyl-, ε-N-butyryl-, and ε-N-crotonyl-lysine containing histone H3 using the pyrrolysine system. Chem. Commun. 49:379–81
    [Google Scholar]
  31. 31. 
    Elsässer SJ, Ernst RJ, Walker OS, Chin JW. 2016. Genetic code expansion in stable cell lines enables encoded chromatin modification. Nat. Methods 13:158–64
    [Google Scholar]
  32. 32. 
    Wilkins BJ, Rall NA, Ostwal Y, Kruitwagen T, Hiragami-Hamada K et al. 2014. A cascade of histone modifications induces chromatin condensation in mitosis. Science 343:77–80
    [Google Scholar]
  33. 33. 
    Kleiner RE, Hang LE, Molloy KR, Chait BT, Kapoor TM. 2018. A chemical proteomics approach to reveal direct protein-protein interactions in living cells. Cell Chem. Biol. 25:110–20
    [Google Scholar]
  34. 34. 
    Yang T, Li X-M, Bao X, Fung YME, Li XD. 2016. Photo-lysine captures proteins that bind lysine post-translational modifications. Nat. Chem. Biol. 12:70–72
    [Google Scholar]
  35. 35. 
    Xie X, Li X-M, Qin F, Lin J, Zhang G et al. 2017. Genetically encoded photoaffinity histone marks. J. Am. Chem. Soc. 139:6522–25
    [Google Scholar]
  36. 36. 
    Dawson PE, Muir TW, Clark-Lewis I, Kent SBH 1994. Synthesis of proteins by native chemical ligation. Science 266:776–79
    [Google Scholar]
  37. 37. 
    Muir TW, Sondhi D, Cole PA 1998. Expressed protein ligation: a general method for protein engineering. PNAS 95:6705–10
    [Google Scholar]
  38. 38. 
    Chang TK, Jackson DY, Burnier JP, Wells JA 1994. Subtiligase: a tool for semisynthesis of proteins. PNAS 91:12544–48
    [Google Scholar]
  39. 39. 
    Mao H, Hart SA, Schink A, Pollok BA. 2004. Sortase-mediated protein ligation: a new method for protein engineering. J. Am. Chem. Soc. 126:2670–71
    [Google Scholar]
  40. 40. 
    Nguyen UTT, Bittova L, Müller MM, Fierz B, David Y et al. 2014. Accelerated chromatin biochemistry using DNA-barcoded nucleosome libraries. Nat. Methods 11:834–40
    [Google Scholar]
  41. 41. 
    Dann GP, Liszczak GP, Bagert JD, Müller MM, Nguyen UTT et al. 2017. ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference. Nature 548:607–11
    [Google Scholar]
  42. 42. 
    Liszczak G, Diehl KL, Dann GP, Muir TW. 2018. Acetylation blocks DNA damage-induced chromatin ADP-ribosylation. Nat. Chem. Biol. 14:837–40
    [Google Scholar]
  43. 43. 
    Wojcik F, Dann GP, Beh LY, Debelouchina GT, Hofmann R, Muir TW. 2018. Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants. Nat. Commun. 9:1394
    [Google Scholar]
  44. 44. 
    Mirzabekov AD, Shick VV, Belyavsky AV, Karpov VL, Bavykin SG. 1978. The structure of nucleosomes: the arrangement of histones in the DNA grooves and along the DNA chain. Cold Spring Harb. Symp. Quant. Biol. 42:149–55
    [Google Scholar]
  45. 45. 
    Lowary PT, Widom J. 1998. New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Mol. Biol. 276:19–42
    [Google Scholar]
  46. 46. 
    Li G, Widom J. 2004. Nucleosomes facilitate their own invasion. Nat. Struct. Mol. Biol. 11:763–69
    [Google Scholar]
  47. 47. 
    Simon M, North JA, Shimko JC, Forties RA, Ferdinand MB et al. 2011. Histone fold modifications control nucleosome unwrapping and disassembly. PNAS 108:12711–16
    [Google Scholar]
  48. 48. 
    Neumann H, Hancock SM, Buning R, Routh A, Chapman L et al. 2009. A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol. Cell 36:153–63
    [Google Scholar]
  49. 49. 
    Poirier MG, Oh E, Tims HS, Widom J. 2009. Dynamics and function of compact nucleosome arrays. Nat. Struct. Mol. Biol. 16:938–44
    [Google Scholar]
  50. 50. 
    Kilic S, Felekyan S, Doroshenko O, Boichenko I, Dimura M et al. 2018. Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1α. Nat. Commun. 9:235
    [Google Scholar]
  51. 51. 
    Fang K, Chen X, Li X, Shen Y, Sun J et al. 2018. Super-resolution imaging of individual human subchromosomal regions in situ reveals nanoscopic building blocks of higher-order structure. ACS Nano 12:4909–18
    [Google Scholar]
  52. 52. 
    Boettiger AN, Bintu B, Moffitt JR, Wang S, Beliveau BJ et al. 2016. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529:418–22
    [Google Scholar]
  53. 53. 
    Bintu B, Mateo LJ, Su J-H, Sinnott-Armstrong NA, Parker M et al. 2018. Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362:eaau1783
    [Google Scholar]
  54. 54. 
    Hocek M. 2019. Enzymatic synthesis of base-functionalized nucleic acids for sensing, cross-linking, and modulation of protein-DNA binding and transcription. Acc. Chem. Res. 52:1730–37
    [Google Scholar]
  55. 55. 
    Smith ZD, Meissner A. 2013. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14:204–20
    [Google Scholar]
  56. 56. 
    Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P et al. 1992. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69:905–14
    [Google Scholar]
  57. 57. 
    Meehan RR, Lewis JD, McKay S, Kleiner EL, Bird AP. 1989. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 58:499–507
    [Google Scholar]
  58. 58. 
    Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H et al. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–35
    [Google Scholar]
  59. 59. 
    Globisch D, Münzel M, Müller M, Michalakis S, Wagner M et al. 2010. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLOS ONE 5:e15367
    [Google Scholar]
  60. 60. 
    Ito S, Shen L, Dai Q, Wu SC, Collins LB et al. 2011. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300–3
    [Google Scholar]
  61. 61. 
    Pfaffeneder T, Hackner B, Truß M, Münzel M, Müller M et al. 2011. The discovery of 5-formylcytosine in embryonic stem cell DNA. Angew. Chem. Int. Ed. 50:7008–12
    [Google Scholar]
  62. 62. 
    Frommer M, McDonald LE, Millar DS, Collis CM, Watt F et al. 1992. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. PNAS 89:1827–31
    [Google Scholar]
  63. 63. 
    Berney M, McGouran JF. 2018. Methods for detection of cytosine and thymine modifications in DNA. Nat. Rev. Chem. 2:332–48
    [Google Scholar]
  64. 64. 
    Song C-X, Szulwach KE, Fu Y, Dai Q, Yi C et al. 2011. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat. Biotechnol. 29:68–75
    [Google Scholar]
  65. 65. 
    Raiber E-A, Beraldi D, Ficz G, Burgess HE, Branco MR et al. 2012. Genome-wide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase. Genome Biol 13:R69
    [Google Scholar]
  66. 66. 
    Ren M, Bai J, Xi Z, Zhou C. 2019. DNA damage in nucleosomes. Sci. China Chem. 62:561–70
    [Google Scholar]
  67. 67. 
    Sczepanski JT, Wong RS, McKnight JN, Bowman GD, Greenberg MM 2010. Rapid DNA-protein cross-linking and strand scission by an abasic site in a nucleosome core particle. PNAS 107:22475–80
    [Google Scholar]
  68. 68. 
    Zhou C, Sczepanski JT, Greenberg MM. 2013. Histone modification via rapid cleavage of C4′-oxidized abasic sites in nucleosome core particles. J. Am. Chem. Soc. 135:5274–77
    [Google Scholar]
  69. 69. 
    Zhou C, Greenberg MM. 2012. Histone-catalyzed cleavage of nucleosomal DNA containing 2-deoxyribonolactone. J. Am. Chem. Soc. 134:8090–93
    [Google Scholar]
  70. 70. 
    Weng L, Greenberg MM. 2015. Rapid histone-catalyzed DNA lesion excision and accompanying protein modification in nucleosomes and nucleosome core particles. J. Am. Chem. Soc. 137:11022–31
    [Google Scholar]
  71. 71. 
    Todd RC, Lippard SJ. 2010. Consequences of cisplatin binding on nucleosome structure and dynamics. Chem. Biol. 17:1334–43
    [Google Scholar]
  72. 72. 
    Zhu G, Song L, Lippard SJ. 2013. Visualizing inhibition of nucleosome mobility and transcription by cisplatin-DNA interstrand crosslinks in live mammalian cells. Cancer Res 73:4451–60
    [Google Scholar]
  73. 73. 
    Núñez ME, Noyes KT, Barton JK. 2002. Oxidative charge transport through DNA in nucleosome core particles. Chem. Biol. 9:403–15
    [Google Scholar]
  74. 74. 
    Davis WB, Bjorklund CC, Deline M. 2012. Probing the effects of DNA-protein interactions on DNA hole transport: The N-terminal histone tails modulate the distribution of oxidative damage and chemical lesions in the nucleosome core particle. Biochemistry 51:3129–42
    [Google Scholar]
  75. 75. 
    Menoni H, Shukla MS, Gerson V, Dimitrov S, Angelov D. 2012. Base excision repair of 8-oxoG in dinucleosomes. Nucleic Acids Res 40:692–700
    [Google Scholar]
  76. 76. 
    Beh LY, Debelouchina GT, Clay DM, Thompson RE, Lindblad KA et al. 2019. Identification of a DNA N6-adenine methyltransferase complex and its impact on chromatin organization. Cell 177:1781–96
    [Google Scholar]
  77. 77. 
    Banerjee DR, Deckard CE, Elinski MB, Buzbee ML, Wang WW et al. 2018. Plug-and-play approach for preparing chromatin containing site-specific DNA modifications: the influence of chromatin structure on base excision repair. J. Am. Chem. Soc. 140:8260–67
    [Google Scholar]
  78. 78. 
    Deckard CE, Banerjee DR, Sczepanski JT. 2019. Chromatin structure and the pioneering transcription factor FOXA1 regulate TDG-mediated removal of 5-formylcytosine from DNA. J. Am. Chem. Soc. 141:14110–14
    [Google Scholar]
  79. 79. 
    Shortt J, Ott CJ, Johnstone RW, Bradner JE. 2017. A chemical probe toolbox for dissecting the cancer epigenome. Nat. Rev. Cancer 17:160–83
    [Google Scholar]
  80. 80. 
    Liu C, Yu Y, Liu F, Wei X, Wrobel JA et al. 2014. A chromatin activity-based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing. Nat. Commun. 5:5733
    [Google Scholar]
  81. 81. 
    Salisbury CM, Cravatt BF 2007. Activity-based probes for proteomic profiling of histone deacetylase complexes. PNAS 104:1171–76
    [Google Scholar]
  82. 82. 
    Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P et al. 2011. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat. Biotechnol. 29:255–68
    [Google Scholar]
  83. 83. 
    Xu C, Soragni E, Chou CJ, Herman D, Plasterer HL et al. 2009. Chemical probes identify a role for histone deacetylase 3 in Friedreich's ataxia gene silencing. Chem. Biol. 16:980–89
    [Google Scholar]
  84. 84. 
    Lau OD, Kundu TK, Soccio RE, Ait-Si-Ali S, Khalil EM et al. 2000. HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol. Cell 5:589–95
    [Google Scholar]
  85. 85. 
    Dose A, Sindlinger J, Bierlmeier J, Bakirbas A, Schulze-Osthoff K et al. 2016. Interrogating substrate selectivity and composition of endogenous histone deacetylase complexes with chemical probes. Angew. Chem. Int. Ed. 55:1192–95
    [Google Scholar]
  86. 86. 
    Dalhoff C, Lukinavičius G, Klimašauskas S, Weinhold E. 2006. Direct transfer of extended groups from synthetic cofactors by DNA methyltransferases. Nat. Chem. Biol. 2:31–32
    [Google Scholar]
  87. 87. 
    Bothwell IR, Islam K, Chen Y, Zheng W, Blum G et al. 2012. Se-adenosyl-l-selenomethionine cofactor analogue as a reporter of protein methylation. J. Am. Chem. Soc. 134:14905–12
    [Google Scholar]
  88. 88. 
    Wang R, Ibáñez G, Islam K, Zheng W, Blum G et al. 2011. Formulating a fluorogenic assay to evaluate S-adenosyl-l-methionine analogues as protein methyltransferase cofactors. Mol. Biosyst. 7:2970–81
    [Google Scholar]
  89. 89. 
    Wang R, Zheng W, Yu H, Deng H, Luo M. 2011. Labeling substrates of protein arginine methyltransferase with engineered enzymes and matched S-adenosyl-l-methionine analogues. J. Am. Chem. Soc. 133:7648–51
    [Google Scholar]
  90. 90. 
    Islam K, Zheng W, Yu H, Deng H, Luo M. 2011. Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling. ACS Chem. Biol. 6:679–84
    [Google Scholar]
  91. 91. 
    Wang R, Islam K, Liu Y, Zheng W, Tang H et al. 2013. Profiling genome-wide chromatin methylation with engineered posttranslation apparatus within living cells. J. Am. Chem. Soc. 135:1048–56
    [Google Scholar]
  92. 92. 
    Yang Y-Y, Hang HC. 2011. Chemical approaches for the detection and synthesis of acetylated proteins. ChemBioChem 12:314–22
    [Google Scholar]
  93. 93. 
    Yang C, Mi J, Feng Y, Ngo L, Gao T et al. 2013. Labeling lysine acetyltransferase substrates with engineered enzymes and functionalized cofactor surrogates. J. Am. Chem. Soc. 135:7791–94
    [Google Scholar]
  94. 94. 
    Hengeveld RCC, Hertz NT, Vromans MJM, Zhang C, Burlingame AL et al. 2012. Development of a chemical genetic approach for human aurora B kinase identifies novel substrates of the chromosomal passenger complex. Mol. Cell. Proteom. 11:47–59
    [Google Scholar]
  95. 95. 
    Spencer DM, Wandless TJ, Schreiber SL, Crabtree GR. 1993. Controlling signal transduction with synthetic ligands. Science 262:1019–24
    [Google Scholar]
  96. 96. 
    Stanton BZ, Chory EJ, Crabtree GR. 2018. Chemically induced proximity in biology and medicine. Science 359:eaao5902
    [Google Scholar]
  97. 97. 
    Hathaway NA, Bell O, Hodges C, Miller EL, Neel DS, Crabtree GR. 2012. Dynamics and memory of heterochromatin in living cells. Cell 149:1447–60
    [Google Scholar]
  98. 98. 
    Erickson BK, Rose CM, Braun CR, Erickson AR, Knott J et al. 2017. A strategy to combine sample multiplexing with targeted proteomics assays for high-throughput protein signature characterization. Mol. Cell 65:361–70
    [Google Scholar]
  99. 99. 
    Kadoch C, Williams RT, Calarco JP, Miller EL, Weber CM et al. 2017. Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states. Nat. Genet. 49:213–22
    [Google Scholar]
  100. 100. 
    Stanton BZ, Hodges C, Calarco JP, Braun SMG, Ku WL et al. 2017. Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin. Nat. Genet. 49:282–88
    [Google Scholar]
  101. 101. 
    Morgan SL, Mariano NC, Bermudez A, Arruda NL, Wu F et al. 2017. Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nat. Commun. 8:15993
    [Google Scholar]
  102. 102. 
    Braun SMG, Kirkland JG, Chory EJ, Husmann D, Calarco JP, Crabtree GR. 2017. Rapid and reversible epigenome editing by endogenous chromatin regulators. Nat. Commun. 8:560
    [Google Scholar]
  103. 103. 
    Ballister ER, Aonbangkhen C, Mayo AM, Lampson MA, Chenoweth DM. 2014. Localized light-induced protein dimerization in living cells using a photocaged dimerizer. Nat. Commun. 5:5475
    [Google Scholar]
  104. 104. 
    Burslem GM, Crews CM. 2020. Proteolysis-targeting chimeras as therapeutics and tools for biological discovery. Cell 181:102–14
    [Google Scholar]
  105. 105. 
    Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ 2001. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. PNAS 98:8554–59
    [Google Scholar]
  106. 106. 
    Schneekloth AR, Pucheault M, Tae HS, Crews CM. 2008. Targeted intracellular protein degradation induced by a small molecule: en route to chemical proteomics. Bioorg. Med. Chem. Lett. 18:5904–8
    [Google Scholar]
  107. 107. 
    Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A et al. 2015. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348:1376–81
    [Google Scholar]
  108. 108. 
    Lu J, Qian Y, Altieri M, Dong H, Wang J et al. 2015. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chem. Biol. 22:755–63
    [Google Scholar]
  109. 109. 
    Vogelmann A, Robaa D, Sippl W, Jung M 2020. Proteolysis targeting chimeras (PROTACs) for epigenetics research. Curr. Opin. Chem. Biol. 57:8–16
    [Google Scholar]
  110. 110. 
    Rothbart SB, Dickson BM, Raab JR, Grzybowski AT, Krajewski K et al. 2015. An interactive database for the assessment of histone antibody specificity. Mol. Cell 59:502–11
    [Google Scholar]
  111. 111. 
    Zhao Y, Garcia BA. 2015. Comprehensive catalog of currently documented histone modifications. Cold Spring Harb. Perspect. Biol. 7:a025064
    [Google Scholar]
  112. 112. 
    Simithy J, Sidoli S, Garcia BA. 2018. Integrating proteomics and targeted metabolomics to understand global changes in histone modifications. Proteomics 18:1700309
    [Google Scholar]
  113. 113. 
    Fan J, Krautkramer KA, Feldman JL, Denu JM. 2015. Metabolic regulation of histone post-translational modifications. ACS Chem. Biol. 10:95–108
    [Google Scholar]
  114. 114. 
    Vermeulen M, Eberl HC, Matarese F, Marks H, Denissov S et al. 2010. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 142:967–80
    [Google Scholar]
  115. 115. 
    Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M, Kouzarides T. 2010. Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 143:470–84
    [Google Scholar]
  116. 116. 
    Li X, Foley EA, Molloy KR, Li Y, Chait BT, Kapoor TM. 2012. Quantitative chemical proteomics approach to identify post-translational modification-mediated protein−protein interactions. J. Am. Chem. Soc. 134:16–19
    [Google Scholar]
  117. 117. 
    Hodge EA, Benhaim MA, Lee KK. 2020. Bridging protein structure, dynamics, and function using hydrogen/deuterium-exchange mass spectrometry. Protein Sci 29:843–55
    [Google Scholar]
  118. 118. 
    Denizio JE, Elsässer SJ, Black BE. 2014. DAXX co-folds with H3.3/H4 using high local stability conferred by the H3.3 variant recognition residues. Nucleic Acids Res 42:4318–31
    [Google Scholar]
  119. 119. 
    Karch KR, Coradin M, Zandarashvili L, Kan Z-Y, Gerace M et al. 2018. Hydrogen-deuterium exchange coupled to top- and middle-down mass spectrometry reveals histone tail dynamics before and after nucleosome assembly. Structure 26:1651–63.e3
    [Google Scholar]
  120. 120. 
    Sanulli S, Trnka MJ, Dharmarajan V, Tibble RW, Pascal BD et al. 2019. HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature 575:390–94
    [Google Scholar]
  121. 121. 
    Böhm V, Hieb AR, Andrews AJ, Gansen A, Rocker A et al. 2011. Nucleosome accessibility governed by the dimer/tetramer interface. Nucleic Acids Res 39:3093–102
    [Google Scholar]
  122. 122. 
    Hall MA, Shundrovsky A, Bai L, Fulbright RM, Lis JT, Wang MD. 2009. High-resolution dynamic mapping of histone-DNA interactions in a nucleosome. Nat. Struct. Mol. Biol. 16:124–29
    [Google Scholar]
  123. 123. 
    Fierz B, Chatterjee C, McGinty RK, Bar-Dagan M, Raleigh DP, Muir TW. 2011. Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction. Nat. Chem. Biol. 7:113–19
    [Google Scholar]
  124. 124. 
    Li W, Chen P, Yu J, Dong L, Liang D et al. 2016. FACT remodels the tetranucleosomal unit of chromatin fibers for gene transcription. Mol. Cell 64:120–33
    [Google Scholar]
  125. 125. 
    Fuller BG, Lampson MA, Foley EA, Rosasco-Nitcher S, Le KV et al. 2008. Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453:1132–36
    [Google Scholar]
  126. 126. 
    Sasaki K, Ito T, Nishino N, Khochbin S, Yoshida M. 2009. Real-time imaging of histone H4 hyperacetylation in living cells. PNAS 106:16257–62
    [Google Scholar]
  127. 127. 
    Lin C-W, Jao CY, Ting AY. 2004. Genetically encoded fluorescent reporters of histone methylation in living cells. J. Am. Chem. Soc. 126:5982–83
    [Google Scholar]
  128. 128. 
    Bracha D, Walls MT, Wei M-T, Zhu L, Kurian M et al. 2018. Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds. Cell 175:1467–80
    [Google Scholar]
  129. 129. 
    Li P, Banjade S, Cheng H-C, Kim S, Chen B et al. 2012. Phase transitions in the assembly of multivalent signalling proteins. Nature 483:336–40
    [Google Scholar]
  130. 130. 
    Jang S, Song J-J. 2019. The big picture of chromatin biology by cryo-EM. Curr. Opin. Struct. Biol. 58:76–87
    [Google Scholar]
  131. 131. 
    Zhou B-R, Feng H, Kato H, Dai L, Yang Y et al. 2013. Structural insights into the histone H1-nucleosome complex. PNAS 110:19390–95
    [Google Scholar]
  132. 132. 
    Zhang W, Tyl M, Ward R, Sobott F, Maman J et al. 2013. Structural plasticity of histones H3-H4 facilitates their allosteric exchange between RbAp48 and ASF1. Nat. Struct. Mol. Biol. 20:29–35
    [Google Scholar]
  133. 133. 
    Rosenzweig R, Kay LE. 2014. Bringing dynamic molecular machines into focus by methyl-TROSY NMR. Annu. Rev. Biochem. 83:291–315
    [Google Scholar]
  134. 134. 
    David Y, Muir TW. 2017. Emerging chemistry strategies for engineering native chromatin. J. Am. Chem. Soc. 139:9090–96
    [Google Scholar]
  135. 135. 
    Li F, Papworth M, Minczuk M, Rohde C, Zhang Y et al. 2007. Chimeric DNA methyltransferases target DNA methylation to specific DNA sequences and repress expression of target genes. Nucleic Acids Res 35:100–12
    [Google Scholar]
  136. 136. 
    Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM et al. 2013. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat. Biotechnol. 31:1137–42
    [Google Scholar]
  137. 137. 
    Snowden AW, Gregory PD, Case CC, Pabo CO. 2002. Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo. Curr. Biol. 12:2159–66
    [Google Scholar]
  138. 138. 
    Kearns NA, Pham H, Tabak B, Genga RM, Silverstein NJ et al. 2015. Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat. Methods 12:401–3
    [Google Scholar]
  139. 139. 
    Hilton IB, D'Ippolito AM, Vockley CM, Thakore PI, Crawford GE et al. 2015. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat. Biotechnol. 33:510–17
    [Google Scholar]
  140. 140. 
    Dervan PB, Edelson BS. 2003. Recognition of the DNA minor groove by pyrrole-imidazole polyamides. Curr. Opin. Struct. Biol. 13:284–99
    [Google Scholar]
  141. 141. 
    Gottesfeld JM, Neely L, Trauger JW, Baird EE, Dervan PB. 1997. Regulation of gene expression by small molecules. Nature 387:202–5
    [Google Scholar]
  142. 142. 
    Mapp AK, Ansari AZ, Ptashne M, Dervan PB 2000. Activation of gene expression by small molecule transcription factors. PNAS 97:3930–35
    [Google Scholar]
  143. 143. 
    Zhao W, Wang Y, Liang F-S. 2020. Chemical and light inducible epigenome editing. Int. J. Mol. Sci. 21:998
    [Google Scholar]
  144. 144. 
    Liszczak GP, Brown ZZ, Kim SH, Oslund RC, David Y, Muir TW 2017. Genomic targeting of epigenetic probes using a chemically tailored Cas9 system. PNAS 114:681–86
    [Google Scholar]
  145. 145. 
    Erwin GS, Grieshop MP, Ali A, Qi J, Lawlor M et al. 2017. Synthetic transcription elongation factors license transcription across repressive chromatin. Science 358:1617–22
    [Google Scholar]
  146. 146. 
    David Y, Vila-Perelló M, Verma S, Muir TW. 2015. Chemical tagging and customizing of cellular chromatin states using ultrafast trans-splicing inteins. Nat. Chem. 7:394–402
    [Google Scholar]
  147. 147. 
    Burton AJ, Haugbro M, Parisi E, Muir TW 2020. Live-cell protein engineering with an ultra-short split intein. PNAS 117:12041–49
    [Google Scholar]
  148. 148. 
    Holt MT, David Y, Pollock S, Tang Z, Jeon J et al. 2015. Identification of a functional hotspot on ubiquitin required for stimulation of methyltransferase activity on chromatin. PNAS 112:10365–70
    [Google Scholar]
  149. 149. 
    Burton AJ, Haugbro M, Gates LA, Bagert JD, Allis CD, Muir TW. 2020. In situ chromatin interactomics using a chemical bait and trap approach. Nat. Chem. 12:520–27
    [Google Scholar]
  150. 150. 
    Chatterjee C, McGinty RK, Pellois J-P, Muir TW. 2007. Auxiliary-mediated site-specific peptide ubiquitylation. Angew. Chem. Int. Ed. 46:2814–18
    [Google Scholar]
  151. 151. 
    McGinty RK, Kim J, Chatterjee C, Roeder RG, Muir TW. 2008. Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation. Nature 453:812–16
    [Google Scholar]
  152. 152. 
    Kim J, Guermah M, McGinty RK, Lee J-S, Tang Z et al. 2009. RAD6-mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 137:459–71
    [Google Scholar]
  153. 153. 
    McGinty RK, Köhn M, Chatterjee C, Chiang KP, Pratt MR, Muir TW. 2009. Structure-activity analysis of semisynthetic nucleosomes: mechanistic insights into the stimulation of Dot1L by ubiquitylated histone H2B. ACS Chem. Biol. 4:958–68
    [Google Scholar]
  154. 154. 
    Chatterjee C, McGinty RK, Fierz B, Muir TW. 2010. Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation. Nat. Chem. Biol. 6:267–69
    [Google Scholar]
  155. 155. 
    Zhou L, Holt MT, Ohashi N, Zhao A, Müller MM et al. 2016. Evidence that ubiquitylated H2B corrals hDot1L on the nucleosomal surface to induce H3K79 methylation. Nat. Commun. 7:10589
    [Google Scholar]
  156. 156. 
    Anderson CJ, Baird MR, Hsu A, Barbour EH, Koyama Y et al. 2019. Structural basis for recognition of ubiquitylated nucleosome by Dot1L methyltransferase. Cell Rep 26:1681–90
    [Google Scholar]
  157. 157. 
    Worden EJ, Hoffmann NA, Hicks CW, Wolberger C. 2019. Mechanism of cross-talk between H2B ubiquitination and H3 methylation by Dot1L. Cell 176:1490–501
    [Google Scholar]
  158. 158. 
    Debelouchina GT, Gerecht K, Muir TW. 2017. Ubiquitin utilizes an acidic surface patch to alter chromatin structure. Nat. Chem. Biol. 13:105–10
    [Google Scholar]
  159. 159. 
    Razin A, Riggs AD. 1980. DNA methylation and gene function. Science 210:604–10
    [Google Scholar]
  160. 160. 
    Mohandas T, Sparkes RS, Shapiro LJ. 1981. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science 211:393–96
    [Google Scholar]
  161. 161. 
    Boyes J, Bird A. 1991. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64:1123–34
    [Google Scholar]
  162. 162. 
    Watt F, Molloy PL. 1988. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 2:1136–43
    [Google Scholar]
  163. 163. 
    Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y 2010. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466:1129–33
    [Google Scholar]
  164. 164. 
    Kohli RM, Zhang Y. 2013. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502:472–79
    [Google Scholar]
  165. 165. 
    Bachman M, Uribe-Lewis S, Yang X, Burgess HE, Iurlaro M et al. 2015. 5-Formylcytosine can be a stable DNA modification in mammals. Nat. Chem. Biol. 11:555–57
    [Google Scholar]
  166. 166. 
    Bachman M, Uribe-Lewis S, Yang X, Williams M, Murrell A, Balasubramanian S 2014. 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat. Chem. 6:1049–55
    [Google Scholar]
  167. 167. 
    Su M, Kirchner A, Stazzoni S, Müller M, Wagner M et al. 2016. 5-Formylcytosine could be a semipermanent base in specific genome sites. Angew. Chem. Int. Ed. 55:11797–800
    [Google Scholar]
  168. 168. 
    Jin S-G, Jiang Y, Qiu R, Rauch TA, Wang Y et al. 2011. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res 71:7360–65
    [Google Scholar]
  169. 169. 
    Vasanthakumar A, Godley LA. 2015. 5-Hydroxymethylcytosine in cancer: significance in diagnosis and therapy. Cancer Genet 208:167–77
    [Google Scholar]
  170. 170. 
    Song C-X, Yin S, Ma L, Wheeler A, Chen Y et al. 2017. 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Res 27:1231–42
    [Google Scholar]
  171. 171. 
    Li W, Zhang X, Lu X, You L, Song Y et al. 2017. 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers. Cell Res 27:1243–57
    [Google Scholar]
  172. 172. 
    Spruijt CG, Gnerlich F, Smits AH, Pfaffeneder T, Jansen PWTC et al. 2013. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives. Cell 152:1146–59
    [Google Scholar]
  173. 173. 
    Iurlaro M, Ficz G, Oxley D, Raiber E-A, Bachman M et al. 2013. A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation. Genome Biol 14:R119
    [Google Scholar]
  174. 174. 
    Mendonca A, Chang EH, Liu W, Yuan C. 2014. Hydroxymethylation of DNA influences nucleosomal conformation and stability in vitro. Biochim. Biophys. Acta Gene Regul. Mech. 1839:1323–29
    [Google Scholar]
  175. 175. 
    Ngo TTM, Yoo J, Dai Q, Zhang Q, He C et al. 2016. Effects of cytosine modifications on DNA flexibility and nucleosome mechanical stability. Nat. Commun. 7:10813
    [Google Scholar]
  176. 176. 
    Song C-X, Szulwach KE, Dai Q, Fu Y, Mao SQ et al. 2013. Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Cell 153:678–91
    [Google Scholar]
  177. 177. 
    Li F, Zhang Y, Bai J, Greenberg MM, Xi Z, Zhou C. 2017. 5-Formylcytosine yields DNA-protein cross-links in nucleosome core particles. J. Am. Chem. Soc. 139:10617–20
    [Google Scholar]
  178. 178. 
    Raiber E-A, Portella G, Cuesta SM, Hardisty R, Murat P et al. 2018. 5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells. Nat. Chem. 10:1258–66
    [Google Scholar]
  179. 179. 
    Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou M-M. 1999. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399:491–96
    [Google Scholar]
  180. 180. 
    Josling GA, Selvarajah SA, Petter M, Duffy MF. 2012. The role of bromodomain proteins in regulating gene expression. Genes 3:320–43
    [Google Scholar]
  181. 181. 
    Shi J, Vakoc CR. 2014. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol. Cell 54:728–36
    [Google Scholar]
  182. 182. 
    Cochran AG, Conery AR, Sims RJ. 2019. Bromodomains: a new target class for drug development. Nat. Rev. Drug Discov. 18:609–28
    [Google Scholar]
  183. 183. 
    Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB et al. 2010. Selective inhibition of BET bromodomains. Nature 468:1067–73
    [Google Scholar]
  184. 184. 
    Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S et al. 2010. Suppression of inflammation by a synthetic histone mimic. Nature 468:1119–23
    [Google Scholar]
  185. 185. 
    Anders L, Guenther MG, Qi J, Fan ZP, Marineau JJ et al. 2014. Genome-wide localization of small molecules. Nat. Biotechnol. 32:92–96
    [Google Scholar]
  186. 186. 
    Li Z, Wang D, Li L, Pan S, Na Z et al. 2014.. “ Minimalist” cyclopropene-containing photo-cross-linkers suitable for live-cell imaging and affinity-based protein labeling. J. Am. Chem. Soc. 136:9990–98
    [Google Scholar]
  187. 187. 
    Baud MGJ, Lin-Shiao E, Cardote T, Tallant C, Pschibul A et al. 2014. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes. Science 346:638–41
    [Google Scholar]
  188. 188. 
    Runcie AC, Zengerle M, Chan K-H, Testa A, van Beurden L et al. 2018. Optimization of a “bump-and-hole” approach to allele-selective BET bromodomain inhibition. Chem. Sci. 9:2452–68
    [Google Scholar]
  189. 189. 
    Zengerle M, Chan K-H, Ciulli A. 2015. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol. 10:1770–77
    [Google Scholar]
  190. 190. 
    Qin C, Hu Y, Zhou B, Fernandez-Salas E, Yang C-Y et al. 2018. Discovery of QCA570 as an exceptionally potent and efficacious proteolysis targeting chimera (PROTAC) degrader of the bromodomain and extra-terminal (BET) proteins capable of inducing complete and durable tumor regression. J. Med. Chem. 61:6685–704
    [Google Scholar]
  191. 191. 
    Zhou B, Hu J, Xu F, Chen Z, Bai L et al. 2018. Discovery of a small-molecule degrader of bromodomain and extra-terminal (BET) proteins with picomolar cellular potencies and capable of achieving tumor regression. J. Med. Chem. 61:462–81
    [Google Scholar]
  192. 192. 
    Reynders M, Matsuura BS, Bérouti M, Simoneschi D, Marzio A et al. 2020. PHOTACs enable optical control of protein degradation. Sci. Adv. 6:eaay5064
    [Google Scholar]
  193. 193. 
    Naro Y, Darrah K, Deiters A. 2020. Optical control of small molecule-induced protein degradation. J. Am. Chem. Soc. 142:2193–97
    [Google Scholar]
  194. 194. 
    Maison C, Almouzni G. 2004. HP1 and the dynamics of heterochromatin maintenance. Nat. Rev. Mol. Cell Biol. 5:296–304
    [Google Scholar]
  195. 195. 
    Canzio D, Chang EY, Shankar S, Kuchenbecker KM, Simon MD et al. 2011. Chromodomain-mediated oligomerization of HP1 suggests a nucleosome-bridging mechanism for heterochromatin assembly. Mol. Cell 41:67–81
    [Google Scholar]
  196. 196. 
    Munari F, Soeroes S, Zenn HM, Schomburg A, Kost N et al. 2012. Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome. J. Biol. Chem. 287:33756–65
    [Google Scholar]
  197. 197. 
    Hiragami-Hamada K, Soeroes S, Nikolov M, Wilkins B, Kreuz S et al. 2016. Dynamic and flexible H3K9me3 bridging via HP1β dimerization establishes a plastic state of condensed chromatin. Nat. Commun. 7:11310
    [Google Scholar]
  198. 198. 
    Müller KP, Erdel F, Caudron-Herger M, Marth C, Fodor BD et al. 2009. Multiscale analysis of dynamics and interactions of heterochromatin protein 1 by fluorescence fluctuation microscopy. Biophys. J. 97:2876–85
    [Google Scholar]
  199. 199. 
    Cheutin T, McNairn AJ, Jenuwein T, Gilbert DM, Singh PB, Misteli T. 2003. Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science 299:721–25
    [Google Scholar]
  200. 200. 
    Kilic S, Bachmann AL, Bryan LC, Fierz B. 2015. Multivalency governs HP1α association dynamics with the silent chromatin state. Nat. Commun. 6:7313
    [Google Scholar]
  201. 201. 
    Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB et al. 2017. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547:236–40
    [Google Scholar]
  202. 202. 
    Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X, Karpen GH. 2017. Phase separation drives heterochromatin domain formation. Nature 547:241–45
    [Google Scholar]
  203. 203. 
    Gibson BA, Doolittle LK, Schneider MWG, Jensen LE, Gamarra N et al. 2019. Organization of chromatin by intrinsic and regulated phase separation. Cell 179:470–84
    [Google Scholar]
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