Establishment of centromere identity is dependent on nuclear spatial organization

• Published in: Current biology Vol. 32; no. 14; pp. 3121 - 3136.e6
• Main Authors: Wu, Weifang, McHugh, Toni, Kelly, David A., Pidoux, Alison L., Allshire, Robin C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 25-07-2022; Cell Press
• Subjects: CENP-A; Centromere - metabolism; centromere identity; Centromere Protein A - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; DNA - genetics; fission yeast; heterochromatin; Heterochromatin - genetics; Heterochromatin - metabolism; Histones - metabolism; S. pombe; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; spatial organization; spindle-pole body; centromere identity; spatial organization; spindle-pole body; S. pombe; fission yeast; CENP-A; heterochromatin
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2022.06.048

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.
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•Episomes bearing heterochromatin localize near fission yeast SPB-centromere clusters•Only centromere DNA inserted near active centromeres assembles CENP-A chromatin•Centromere DNA directly tethered to the SPB assembles CENP-A chromatin•Nuclear position is an epigenetic factor that influences centromere identity
Wu et al. show that heterochromatin tends to associate with fission yeast spindle-pole bodies (SPBs) where centromeres cluster. The requirement for heterochromatin in CENP-A/kinetochore establishment on centromeric DNA is bypassed by placing or tethering centromeric DNA near SPB-centromere clusters. Thus, nuclear positioning influences centromere identity.