1. Establishment of centromere identity is dependent on nuclear spatial organization.
- Author
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Wu, Weifang, McHugh, Toni, Kelly, David A., Pidoux, Alison L., and Allshire, Robin C.
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CENTROMERE , *HETEROCHROMATIN , *CHROMATIN , *EPISOMES , *DNA , *YEAST - Abstract
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. [Display omitted] • 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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