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CENP-A and CENP-B collaborate to create an open centromeric chromatin state

Author

Listed:
  • Harsh Nagpal

    (SB ISIC LCBM)

  • Ahmad Ali-Ahmad

    (University of Oslo)

  • Yasuhiro Hirano

    (Osaka University)

  • Wei Cai

    (SB ISIC LCBM)

  • Mario Halic

    (St. Jude Children’s Research Hospital)

  • Tatsuo Fukagawa

    (Osaka University)

  • Nikolina Sekulić

    (University of Oslo
    University of Oslo)

  • Beat Fierz

    (SB ISIC LCBM)

Abstract

Centromeres are epigenetically defined via the presence of the histone H3 variant CENP-A. Contacting CENP-A nucleosomes, the constitutive centromere associated network (CCAN) and the kinetochore assemble, connecting the centromere to spindle microtubules during cell division. The DNA-binding centromeric protein CENP-B is involved in maintaining centromere stability and, together with CENP-A, shapes the centromeric chromatin state. The nanoscale organization of centromeric chromatin is not well understood. Here, we use single-molecule fluorescence and cryoelectron microscopy (cryoEM) to show that CENP-A incorporation establishes a dynamic and open chromatin state. The increased dynamics of CENP-A chromatin create an opening for CENP-B DNA access. In turn, bound CENP-B further opens the chromatin fiber structure and induces nucleosomal DNA unwrapping. Finally, removal of CENP-A increases CENP-B mobility in cells. Together, our studies show that the two centromere-specific proteins collaborate to reshape chromatin structure, enabling the binding of centromeric factors and establishing a centromeric chromatin state.

Suggested Citation

  • Harsh Nagpal & Ahmad Ali-Ahmad & Yasuhiro Hirano & Wei Cai & Mario Halic & Tatsuo Fukagawa & Nikolina Sekulić & Beat Fierz, 2023. "CENP-A and CENP-B collaborate to create an open centromeric chromatin state," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43739-5
    DOI: 10.1038/s41467-023-43739-5
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    References listed on IDEAS

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