Establishment of centromere identity is dependent on nuclear spatial organization

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP-ACnp1 incorporation, but their use is context dependent, requiring adjacent heterochromatin. CENP-ACnp1 overexpression bypasses heterochromatin dependency, suggesting that heterochromatin ensures exposure to conditions or locations permissive for CENP-ACnp1 assembly. Centromeres cluster around spindle-pole bodies (SPBs). We show that heterochromatin-bearing minichromosomes localize close to SPBs, consistent with this location promoting CENP-ACnp1 incorporation. We demonstrate that heterochromatin-independent de novo CENP-ACnp1 chromatin assembly occurs when central domain DNA is placed near, but not far from, endogenous centromeres or neocentromeres. Moreover, direct tethering of central domain DNA at SPBs permits CENP-ACnp1 assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-ACnp1 incorporation because target sequences are exposed to high levels of CENP-ACnp1 and associated assembly factors. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity.
Original languageEnglish
Pages (from-to)3121-3136.e6
Number of pages16
JournalCurrent Biology
Issue number14
Early online date12 Jul 2022
Publication statusPublished - 25 Jul 2022

Keywords / Materials (for Non-textual outputs)

  • centromere identity
  • CENP-A
  • spindle-pole body
  • heterochromatin
  • spatial organization
  • fission yeast
  • S. pombe


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