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Live Cell Synthetic Histone Acetylation by Chemical Catalyst

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Chromosome Analysis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2519))

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Abstract

Posttranslational modifications (PTMs) of histones, such as lysine acetylation and ubiquitination, regulate chromatin structure and gene expression. In living organisms, histone PTMs are catalyzed by histone-modifying enzymes. Here, we describe an entirely chemical method to introduce histone modifications in living cells without genetic manipulation. The chemical catalyst PEG-LANA-DSSMe activates a thioester acetyl donor, N,S-diacetylcysteamine (NAC-Ac), and promotes regioselective, synthetic histone acetylation at H2BK120 in living cells.

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References

  1. Hyun K, Jeon J, Park K, Kim J (2017) Writing, erasing and reading histone lysine methylations. Exp Mol Med 49(4):e324. https://doi.org/10.1038/emm.2017.11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mirabella AC, Foster BM, Bartke T (2016) Chromatin deregulation in disease. Chromosoma 125(1):75–93. https://doi.org/10.1007/s00412-015-0530-0

    Article  CAS  PubMed  Google Scholar 

  3. Roadmap Epigenomics C, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi S, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Neph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M (2015) Integrative analysis of 111 reference human epigenomes. Nature 518(7539):317–330. https://doi.org/10.1038/nature14248

    Article  CAS  Google Scholar 

  4. Yamatsugu K, Kawashima SA, Kanai M (2018) Leading approaches in synthetic epigenetics for novel therapeutic strategies. Curr Opin Chem Biol 46:10–17. https://doi.org/10.1016/j.cbpa.2018.03.011

    Article  CAS  PubMed  Google Scholar 

  5. Muller MM, Muir TW (2015) Histones: at the crossroads of peptide and protein chemistry. Chem Rev 115(6):2296–2349. https://doi.org/10.1021/cr5003529

    Article  CAS  PubMed  Google Scholar 

  6. 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(5):394–402. https://doi.org/10.1038/nchem.2224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wright TH, Bower BJ, Chalker JM, Bernardes GJL, Wiewiora R, Ng WL, Raj R, Faulkner S, Vallee MRJ, Phanumartwiwath A, Coleman OD, Thezenas ML, Khan M, Galan SRG, Lercher L, Schombs MW, Gerstberger S, Palm-Espling ME, Baldwin AJ, Kessler BM, Claridge TDW, Mohammed S, Davis BG (2016) Posttranslational mutagenesis: a chemical strategy for exploring protein side-chain diversity. Science 354(6312) doi:ARTN aag1465. https://doi.org/10.1126/science.aag1465

  8. Yang A, Ha S, Ahn J, Kim R, Kim S, Lee Y, Kim J, Söll D, Lee HY, Park HS (2016) A chemical biology route to site-specific authentic protein modifications. Science 354(6312):623–626. https://doi.org/10.1126/science.aah4428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ishiguro T, Amamoto Y, Tanabe K, Liu J, Kajino H, Fujimura A, Aoi Y, Osakabe A, Horikoshi N, Kurumizaka H, Yamatsugu K, Kawashima SA, Kanai M (2017) Synthetic chromatin acylation by an artificial catalyst system. Chem-Us 2(6):840–859. https://doi.org/10.1016/j.chempr.2017.04.002

    Article  CAS  Google Scholar 

  10. Amamoto Y, Aoi Y, Nagashima N, Suto H, Yoshidome D, Arimura Y, Osakabe A, Kato D, Kurumizaka H, Kawashima SA, Yamatsugu K, Kanai M (2017) Synthetic posttranslational modifications: chemical catalyst-driven regioselective histone acylation of native chromatin. J Am Chem Soc 139(22):7568–7576. https://doi.org/10.1021/jacs.7b02138

    Article  CAS  PubMed  Google Scholar 

  11. Kajino H, Nagatani T, Oi M, Kujirai T, Kurumizaka H, Nishiyama A, Nakanishi M, Yamatsugu K, Kawashima SA, Kanai M (2020) Synthetic hyperacetylation of nucleosomal histones. RSC Chem Biol 1(2):56–59. https://doi.org/10.1039/D0CB00029A

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fujiwara Y, Yamanashi Y, Fujimura A, Sato Y, Kujirai T, Kurumizaka H, Kimura H, Yamatsugu K, Kawashima SA, Kanai M (2021) Live-cell epigenome manipulation by synthetic histone acetylation catalyst system. Proc Natl Acad Sci U S A 118(4). https://doi.org/10.1073/pnas.2019554118

  13. Kulkarni RA, Worth AJ, Zengeya TT, Shrimp JH, Garlick JM, Roberts AM, Montgomery DC, Sourbier C, Gibbs BK, Mesaros C, Tsai YC, Das S, Chan KC, Zhou M, Andresson T, Weissman AM, Linehan WM, Blair IA, Snyder NW, Meier JL (2017) Discovering targets of non-enzymatic acylation by thioester reactivity profiling. Cell Chem Biol 24(2):231–242. https://doi.org/10.1016/j.chembiol.2017.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sato Y, Stasevich TJ, Kimura H (2018) Visualizing the dynamics of inactive X chromosomes in living cells using antibody-based fluorescent probes. Methods Mol Biol 1861:91–102. https://doi.org/10.1007/978-1-4939-8766-5_8

    Article  CAS  PubMed  Google Scholar 

  15. Hamajima W, Fujimura A, Fujiwara Y, Yamatsugu K, Kawashima SA, Kanai M (2019) Site-selective synthetic acylation of a target protein in living cells promoted by a chemical catalyst/donor system. ACS Chem Biol 14(6):1102–1109. https://doi.org/10.1021/acschembio.9b00102

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    Shigehiro A. Kawashima & Motomu Kanai

Authors
  1. Shigehiro A. Kawashima
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  2. Motomu Kanai
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Editor information

Editors and Affiliations

  1. Division of Diagnostic Imaging, Department of Radiology, Japan Labour Health and Safety Organization, Tokyo Rosai Hospital, Ohta-ku, Tokyo, Japan

    Eisuke Gotoh

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© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Kawashima, S.A., Kanai, M. (2023). Live Cell Synthetic Histone Acetylation by Chemical Catalyst. In: Gotoh, E. (eds) Chromosome Analysis. Methods in Molecular Biology, vol 2519. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2433-3_17

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  • DOI: https://doi.org/10.1007/978-1-0716-2433-3_17

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2432-6

  • Online ISBN: 978-1-0716-2433-3

  • eBook Packages: Springer Protocols

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