Centromere DNA destabilizes H3 nucleosomes to promote CENP-A deposition during the cell cycle

Manu Shukla, Pin Tong, Sharon A. White, Puneet P. Singh, Angus M. Reid, Sandra Catania, Alison L. Pidoux, Robin C. Allshire

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Active centromeres are defined by the presence of nucleosomes containing CENP-A, a histone H3 variant, which alone is sufficient to direct kinetochore assembly. Once assembled at a location CENP-A chromatin and kinetochores are maintained at that location through a positive feedback loop where kinetochore proteins recruited by CENP-A promote deposition of new CENP-A following replication. Although CENP-A chromatin itself is a heritable entity, it is normally associated with specific sequences. Intrinsic properties of centromeric DNA may favour the assembly of CENP-A rather than H3 nucleosomes. Here we investigate histone dynamics on centromeric DNA. We show that during S-phase histone H3 is deposited as a placeholder at fission yeast centromeres and is subsequently evicted in G2 when we detect deposition of the majority of new CENP-ACnp1. We also find that centromeric DNA has an innate property of driving high rates of turnover of H3-containing nucleosomes, resulting in low nucleosome occupancy. When placed at an ectopic chromosomal location in the absence of any CENP-ACnp1 assembly, centromeric DNA appears to retain its ability to impose S-phase deposition and G2 eviction of H3, suggesting that features within centromeric DNA program H3 dynamics. As (RNAPII) occupancy on this centromere DNA coincides with H3 eviction in G2, we propose a model in which RNAPII-coupled chromatin remodeling promotes replacement of H3 with CENP-ACnp1 nucleosomes.
Original languageEnglish
Pages (from-to)3924-3936
Number of pages17
JournalCurrent Biology
Issue number24
Early online date29 Nov 2018
Publication statusPublished - 17 Dec 2018

Keywords / Materials (for Non-textual outputs)

  • centromere
  • CENP-A
  • transcription
  • nucleosome
  • S. pombe
  • kinetochore
  • chromosome
  • fission yeast
  • cell cycle


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