Establishment of centromere identity is dependent on nuclear spatial organization.

Autor: Wu W; Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK., McHugh T; Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK., Kelly DA; Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK., Pidoux AL; Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK., Allshire RC; Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK. Electronic address: robin.allshire@ed.ac.uk.
Jazyk: angličtina
Zdroj: Current biology : CB [Curr Biol] 2022 Jul 25; Vol. 32 (14), pp. 3121-3136.e6. Date of Electronic Publication: 2022 Jul 12.
DOI: 10.1016/j.cub.2022.06.048
Abstrakt: 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-A Cnp1 incorporation, but their use is context dependent, requiring adjacent heterochromatin. CENP-A Cnp1 overexpression bypasses heterochromatin dependency, suggesting that heterochromatin ensures exposure to conditions or locations permissive for CENP-A Cnp1 assembly. Centromeres cluster around spindle-pole bodies (SPBs). We show that heterochromatin-bearing minichromosomes localize close to SPBs, consistent with this location promoting CENP-A Cnp1 incorporation. We demonstrate that heterochromatin-independent de novo CENP-A Cnp1 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-A Cnp1 assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-A Cnp1 incorporation because target sequences are exposed to high levels of CENP-A Cnp1 and associated assembly factors. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE