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Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase.

<div class='caption-title'>Cryo-EM structures of the SET8–NCP and SET8–NCPCENP-A complexes.</div>
<div class='caption-title'>Preparation of the SET8–NCP and SET8–NCPCENP-A complexes.</div>
<div class='caption-title'>Cryo-EM processing of the SET8–NCP and SET8–NCPCENP-A complexes.</div>
Ho CH, Takizawa Y, Kobayashi W, Arimura Y, Kimura H, Kurumizaka H
OpenAccess logo Life Sci Alliance 4 (2021)
Cited: 12 times
EuropePMC logo PMID: 33574035

Abstract

SET8 is solely responsible for histone H4 lysine-20 (H4K20) monomethylation, which preferentially occurs in nucleosomal H4. However, the underlying mechanism by which SET8 specifically promotes the H4K20 monomethylation in the nucleosome has not been elucidated. Here, we report the cryo-EM structures of the human SET8-nucleosome complexes with histone H3 and the centromeric H3 variant, CENP-A. Surprisingly, we found that the overall cryo-EM structures of the SET8-nucleosome complexes are substantially different from the previous crystal structure models. In the complexes with H3 and CENP-A nucleosomes, SET8 specifically binds the nucleosomal acidic patch via an arginine anchor, composed of the Arg188 and Arg192 residues. Mutational analyses revealed that the interaction between the SET8 arginine anchor and the nucleosomal acidic patch plays an essential role in the H4K20 monomethylation activity. These results provide the groundwork for understanding the mechanism by which SET8 specifically accomplishes the H4K20 monomethylation in the nucleosome.

Reviews - 7d1z mentioned but not cited (2)

  1. Principles of nucleosome recognition by chromatin factors and enzymes. McGinty RK, Tan S. Curr Opin Struct Biol 71 16-26 (2021)
  2. The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications. Li Y, Ge K, Li T, Cai R, Chen Y. Protein Cell 14 165-179 (2023)

Articles - 7d1z mentioned but not cited (2)

  1. Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase. Ho CH, Takizawa Y, Kobayashi W, Arimura Y, Kimura H, Kurumizaka H. Life Sci Alliance 4 e202000919 (2021)
  2. Determination of Histone Methyltransferase Structures in Complex with the Nucleosome by Cryogenic Electron Microscopy. Spangler CJ, McGinty RK. Methods Mol Biol 2529 149-168 (2022)


Reviews citing this publication (2)

  1. Is There a Histone Code for Cellular Quiescence? Bonitto K, Sarathy K, Atai K, Mitra M, Coller HA. Front Cell Dev Biol 9 739780 (2021)
  2. Structural studies of functional nucleosome complexes with transacting factors. Kurumizaka H. Proc Jpn Acad Ser B Phys Biol Sci 98 1-14 (2022)

Articles citing this publication (6)

  1. Structural features of nucleosomes in interphase and metaphase chromosomes. Arimura Y, Shih RM, Froom R, Funabiki H. Mol Cell 81 4377-4397.e12 (2021)
  2. Cryo-EM structure of the nucleosome core particle containing Giardia lamblia histones. Sato S, Takizawa Y, Hoshikawa F, Dacher M, Tanaka H, Tachiwana H, Kujirai T, Iikura Y, Ho CH, Adachi N, Patwal I, Flaus A, Kurumizaka H. Nucleic Acids Res 49 8934-8946 (2021)
  3. Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity. Budziszewski GR, Zhao Y, Spangler CJ, Kedziora KM, Williams MR, Azzam DN, Skrajna A, Koyama Y, Cesmat AP, Simmons HC, Arteaga EC, Strauss JD, Kireev D, McGinty RK. Nucleic Acids Res 50 4355-4371 (2022)
  4. DOT1L regulates chromatin reorganization and gene expression during sperm differentiation. Blanco M, El Khattabi L, Gobé C, Crespo M, Coulée M, de la Iglesia A, Ialy-Radio C, Lapoujade C, Givelet M, Delessard M, Seller-Corona I, Yamaguchi K, Vernet N, Van Leeuwen F, Lermine A, Okada Y, Daveau R, Oliva R, Fouchet P, Ziyyat A, Pflieger D, Cocquet J. EMBO Rep 24 e56316 (2023)
  5. Oocyte-Specific Knockout of Histone Lysine Demethylase KDM2a Compromises Fertility by Blocking the Development of Follicles and Oocytes. Xiong X, Zhang X, Yang M, Zhu Y, Yu H, Fei X, Mastuda F, Lan D, Xiong Y, Fu W, Yin S, Li J. Int J Mol Sci 23 12008 (2022)
  6. Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase. Lin F, Zhang R, Shao W, Lei C, Ma M, Zhang Y, Wen Z, Li W. Cell Discov 9 120 (2023)


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