The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA

Kozo Takeuchi, Tatsuya Nishino, Kouta Mayanagi, Naoki Horikoshi, Akihisa Osakabe, Hiroaki Tachiwana, Tetsuya Hori, Hitoshi Kurumizaka, Tatsuo Fukagawa

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The centromere is a specific genomic region upon which the kinetochore is formed to attach to spindle microtubules for faithful chromosome segregation. To distinguish this chromosomal region from other genomic loci, the centromere contains a specific chromatin structure including specialized nucleosomes containing the histone H3 variant CENP-A. In addition to CENP-A nucleosomes, we have found that centromeres contain a nucleosome-like structure comprised of the histone-fold CENP-T-W-S-X complex. However, it is unclear how the CENP-T-W-S-X complex associates with centromere chromatin. Here, we demonstrate that the CENP-T-W-S-X complex binds preferentially to ∼100 bp of linker DNA rather than nucleosome-bound DNA. In addition, we find that the CENP-T-W-S-X complex primarily binds to DNA as a (CENP-T-W-S-X)2 structure. Interestingly, in contrast to canonical nucleosomes that negatively supercoil DNA, the CENP-T-W-S-X complex induces positive DNA supercoils. We found that the DNA-binding regions in CENP-T or CENP-W, but not CENP-S or CENP-X, are required for this positive supercoiling activity and the kinetochore targeting of the CENP-T-W-S-X complex. In summary, our work reveals the structural features and properties of the CENP-T-W-S-X complex for its localization to centromeres.

Original languageEnglish
Pages (from-to)1644-1655
Number of pages12
JournalNucleic Acids Research
Volume42
Issue number3
DOIs
Publication statusPublished - 2014 Feb

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Nucleosomes
Centromere
DNA
Kinetochores
Histones
Chromatin
Chromosome Segregation
Microtubules
centromere protein A

ASJC Scopus subject areas

  • Genetics

Cite this

Takeuchi, K., Nishino, T., Mayanagi, K., Horikoshi, N., Osakabe, A., Tachiwana, H., ... Fukagawa, T. (2014). The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. Nucleic Acids Research, 42(3), 1644-1655. https://doi.org/10.1093/nar/gkt1124

The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. / Takeuchi, Kozo; Nishino, Tatsuya; Mayanagi, Kouta; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Hori, Tetsuya; Kurumizaka, Hitoshi; Fukagawa, Tatsuo.

In: Nucleic Acids Research, Vol. 42, No. 3, 02.2014, p. 1644-1655.

Research output: Contribution to journalArticle

Takeuchi, K, Nishino, T, Mayanagi, K, Horikoshi, N, Osakabe, A, Tachiwana, H, Hori, T, Kurumizaka, H & Fukagawa, T 2014, 'The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA', Nucleic Acids Research, vol. 42, no. 3, pp. 1644-1655. https://doi.org/10.1093/nar/gkt1124
Takeuchi K, Nishino T, Mayanagi K, Horikoshi N, Osakabe A, Tachiwana H et al. The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. Nucleic Acids Research. 2014 Feb;42(3):1644-1655. https://doi.org/10.1093/nar/gkt1124
Takeuchi, Kozo ; Nishino, Tatsuya ; Mayanagi, Kouta ; Horikoshi, Naoki ; Osakabe, Akihisa ; Tachiwana, Hiroaki ; Hori, Tetsuya ; Kurumizaka, Hitoshi ; Fukagawa, Tatsuo. / The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 3. pp. 1644-1655.
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AU - Osakabe, Akihisa

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