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Centromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition

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  • Lucie Y. Guo

    (Perelman School of Medicine, University of Pennsylvania
    Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania)

  • Praveen Kumar Allu

    (Perelman School of Medicine, University of Pennsylvania)

  • Levani Zandarashvili

    (Perelman School of Medicine, University of Pennsylvania)

  • Kara L. McKinley

    (Massachusetts Institute of Technology)

  • Nikolina Sekulic

    (Perelman School of Medicine, University of Pennsylvania
    Present address: Norwegian Centre for Molecular Medicine and Department of Chemistry, University of Oslo, Oslo 0349, Norway)

  • Jennine M. Dawicki-McKenna

    (Perelman School of Medicine, University of Pennsylvania)

  • Daniele Fachinetti

    (University of California, San Diego
    Present address: Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, Paris F-75005, France)

  • Glennis A. Logsdon

    (Perelman School of Medicine, University of Pennsylvania
    Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania)

  • Ryan M. Jamiolkowski

    (Graduate Program in Bioengineering, University of Pennsylvania)

  • Don W. Cleveland

    (University of California, San Diego)

  • Iain M. Cheeseman

    (Massachusetts Institute of Technology)

  • Ben E. Black

    (Perelman School of Medicine, University of Pennsylvania
    Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania)

Abstract

Maintaining centromere identity relies upon the persistence of the epigenetic mark provided by the histone H3 variant, centromere protein A (CENP-A), but the molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define the contributions of each of the three candidate CENP-A nucleosome-binding domains (two on CENP-C and one on CENP-N) to CENP-A stability using gene replacement and rapid protein degradation. Surprisingly, the most conserved domain, the CENP-C motif, is dispensable. Instead, the stability is conferred by the unfolded central domain of CENP-C and the folded N-terminal domain of CENP-N that becomes rigidified 1,000-fold upon crossbridging CENP-A and its adjacent nucleosomal DNA. Disrupting the ‘arginine anchor’ on CENP-C for the nucleosomal acidic patch disrupts the CENP-A nucleosome structural transition and removes CENP-A nucleosomes from centromeres. CENP-A nucleosome retention at centromeres requires a core centromeric nucleosome complex where CENP-C clamps down a stable nucleosome conformation and CENP-N fastens CENP-A to the DNA.

Suggested Citation

  • Lucie Y. Guo & Praveen Kumar Allu & Levani Zandarashvili & Kara L. McKinley & Nikolina Sekulic & Jennine M. Dawicki-McKenna & Daniele Fachinetti & Glennis A. Logsdon & Ryan M. Jamiolkowski & Don W. Cl, 2017. "Centromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15775
    DOI: 10.1038/ncomms15775
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    Cited by:

    1. Christian Hoischen & Sibel Yavas & Thorsten Wohland & Stephan Diekmann, 2018. "CENP-C/H/I/K/M/T/W/N/L and hMis12 but not CENP-S/X participate in complex formation in the nucleoplasm of living human interphase cells outside centromeres," PLOS ONE, Public Library of Science, vol. 13(3), pages 1-26, March.

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