Chromosome segregation during cell division is driven by mitotic spindle attachment to the centromere region on each chromosome. Centromeres form a protein scaffold defined by chromatin featuring CENP-A, a conserved histone H3 variant, in a manner largely independent of local DNA cis elements. CENP-A nucleosomes fulfill two essential criteria to epigenetically identify the centromere. They undergo self-templated duplication to reestablish centromeric chromatin following DNA replication. More importantly, CENP-A incorporated into centromeric chromatin is stably transmitted through consecutive cell division cycles. CENP-A nucleosomes have unique structural properties and binding partners that potentially explain their long lifetime in vivo. However, rather than a static building block, centromeric chromatin is dynamically regulated throughout the cell cycle, indicating that CENP-A stability is also controlled by external factors. We discuss recent insights and identify the outstanding questions on how dynamic control of the long-term stability of CENP-A ensures epigenetic centromere inheritance.
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5 October 2020
Review|
September 15 2020
Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control
Sreyoshi Mitra,
Sreyoshi Mitra
1
Department of Biochemistry, University of Oxford, Oxford, UK
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Bharath Srinivasan,
Bharath Srinivasan
2
Mechanistic Biology and Profiling, Discovery Sciences, R&D, AstraZeneca, Cambridge, UK
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Lars E.T. Jansen
1
Department of Biochemistry, University of Oxford, Oxford, UK
Correspondence to Lars E.T. Jansen: lars.jansen@bioch.ox.ac.uk
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Sreyoshi Mitra
1
Department of Biochemistry, University of Oxford, Oxford, UK
Bharath Srinivasan
2
Mechanistic Biology and Profiling, Discovery Sciences, R&D, AstraZeneca, Cambridge, UK
Lars E.T. Jansen
1
Department of Biochemistry, University of Oxford, Oxford, UK
Correspondence to Lars E.T. Jansen: lars.jansen@bioch.ox.ac.uk
Received:
May 13 2020
Revision Received:
August 08 2020
Accepted:
August 12 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
© 2020 Mitra et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2020) 219 (10): e202005099.
Article history
Received:
May 13 2020
Revision Received:
August 08 2020
Accepted:
August 12 2020
Citation
Sreyoshi Mitra, Bharath Srinivasan, Lars E.T. Jansen; Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control. J Cell Biol 5 October 2020; 219 (10): e202005099. doi: https://doi.org/10.1083/jcb.202005099
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