Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome

Yasuhiro Arimura, Masae Ikura, Risa Fujita, Mamiko Noda, Wataru Kobayashi, Naoki Horikoshi, Jiying Sun, Lin Shi, Masayuki Kusakabe, Masahiko Harata, Yasuyuki Ohkawa, Satoshi Tashiro, Hiroshi Kimura, Tsuyoshi Ikura, Hitoshi Kurumizaka

研究成果: ジャーナルへの寄稿記事

6 引用 (Scopus)

抄録

Mutations of the Glu76 residue of canonical histone H2B are frequently found in cancer cells. However, it is quite mysterious how a single amino acid substitution in one of the multiple H2B genes affects cell fate. Here we found that the H2B E76K mutation, in which Glu76 is replaced by Lys (E76K), distorted the interface between H2B and H4 in the nucleosome, as revealed by the crystal structure and induced nucleosome instability in vivo and in vitro. Exogenous production of the H2B E76Kmutant robustly enhanced the colony formation ability of the expressing cells, indicating that the H2B E76K mutant has the potential to promote oncogenic transformation in the presence of wild-type H2B. We found that other cancer-associated mutations of histones, H3.1 E97K and H2A.Z.1 R80C, also induced nucleosome instability. Interestingly, like the H2B E76K mutant, the H3.1 E97K mutant was minimally incorporated into chromatin in cells, but it enhanced the colony formation ability. In contrast, the H2A.Z.1 R80C mutant was incorporated into chromatin in cells, and had minor effects on the colony formation ability of the cells. These characteristics of histones with cancerassociated mutations may provide important information toward understanding how themutations promote cancer progression.

元の言語英語
ページ(範囲)10007-10018
ページ数12
ジャーナルNucleic acids research
46
発行部数19
DOI
出版物ステータス出版済み - 1 1 2018

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Nucleosomes
Histones
Mutation
Neoplasms
Chromatin
Amino Acid Substitution
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Arimura, Y., Ikura, M., Fujita, R., Noda, M., Kobayashi, W., Horikoshi, N., ... Kurumizaka, H. (2018). Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome. Nucleic acids research, 46(19), 10007-10018. https://doi.org/10.1093/nar/gky661

Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome. / Arimura, Yasuhiro; Ikura, Masae; Fujita, Risa; Noda, Mamiko; Kobayashi, Wataru; Horikoshi, Naoki; Sun, Jiying; Shi, Lin; Kusakabe, Masayuki; Harata, Masahiko; Ohkawa, Yasuyuki; Tashiro, Satoshi; Kimura, Hiroshi; Ikura, Tsuyoshi; Kurumizaka, Hitoshi.

:: Nucleic acids research, 巻 46, 番号 19, 01.01.2018, p. 10007-10018.

研究成果: ジャーナルへの寄稿記事

Arimura, Y, Ikura, M, Fujita, R, Noda, M, Kobayashi, W, Horikoshi, N, Sun, J, Shi, L, Kusakabe, M, Harata, M, Ohkawa, Y, Tashiro, S, Kimura, H, Ikura, T & Kurumizaka, H 2018, 'Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome', Nucleic acids research, 巻. 46, 番号 19, pp. 10007-10018. https://doi.org/10.1093/nar/gky661
Arimura, Yasuhiro ; Ikura, Masae ; Fujita, Risa ; Noda, Mamiko ; Kobayashi, Wataru ; Horikoshi, Naoki ; Sun, Jiying ; Shi, Lin ; Kusakabe, Masayuki ; Harata, Masahiko ; Ohkawa, Yasuyuki ; Tashiro, Satoshi ; Kimura, Hiroshi ; Ikura, Tsuyoshi ; Kurumizaka, Hitoshi. / Cancer-associated mutations of histones H2B, H3.1 and H2A.Z.1 affect the structure and stability of the nucleosome. :: Nucleic acids research. 2018 ; 巻 46, 番号 19. pp. 10007-10018.
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abstract = "Mutations of the Glu76 residue of canonical histone H2B are frequently found in cancer cells. However, it is quite mysterious how a single amino acid substitution in one of the multiple H2B genes affects cell fate. Here we found that the H2B E76K mutation, in which Glu76 is replaced by Lys (E76K), distorted the interface between H2B and H4 in the nucleosome, as revealed by the crystal structure and induced nucleosome instability in vivo and in vitro. Exogenous production of the H2B E76Kmutant robustly enhanced the colony formation ability of the expressing cells, indicating that the H2B E76K mutant has the potential to promote oncogenic transformation in the presence of wild-type H2B. We found that other cancer-associated mutations of histones, H3.1 E97K and H2A.Z.1 R80C, also induced nucleosome instability. Interestingly, like the H2B E76K mutant, the H3.1 E97K mutant was minimally incorporated into chromatin in cells, but it enhanced the colony formation ability. In contrast, the H2A.Z.1 R80C mutant was incorporated into chromatin in cells, and had minor effects on the colony formation ability of the cells. These characteristics of histones with cancerassociated mutations may provide important information toward understanding how themutations promote cancer progression.",
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AU - Arimura, Yasuhiro

AU - Ikura, Masae

AU - Fujita, Risa

AU - Noda, Mamiko

AU - Kobayashi, Wataru

AU - Horikoshi, Naoki

AU - Sun, Jiying

AU - Shi, Lin

AU - Kusakabe, Masayuki

AU - Harata, Masahiko

AU - Ohkawa, Yasuyuki

AU - Tashiro, Satoshi

AU - Kimura, Hiroshi

AU - Ikura, Tsuyoshi

AU - Kurumizaka, Hitoshi

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