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

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    44 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 - Feb 2014

    All Science Journal Classification (ASJC) codes

    • Genetics

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  • Cite this

    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, 42(3), 1644-1655. https://doi.org/10.1093/nar/gkt1124