Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential
Name
nihms-1535866.pdf
Description
Accepted version
Size
3.32 MB
Format
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Checksum (MD5)
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Author(s)
Swartz, S. Zachary
McKay, Liliana S.
Su, Kuan-Chung
Bury, Leah
Padeganeh, Abbas
Maddox, Paul S.
Knouse, Kristin A.
Cheeseman, Iain M
Date Issued
October 2019
Journal
Developmental Cell
Publisher
Elsevier BV
Citation
Swartz, S. Zachary et al. "Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential." Developmental Cell 51, 1 (October 2019): P35-48.e7 © 2019 Elsevier Inc
Version
Author's final manuscript
Abstract
Centromeres provide a robust model for epigenetic inheritance as they are specified by sequence-independent mechanisms involving the histone H3-variant centromere protein A (CENP-A). Prevailing models indicate that the high intrinsic stability of CENP-A nucleosomes maintains centromere identity indefinitely. Here, we demonstrate that CENP-A is not stable at centromeres but is instead gradually and continuously incorporated in quiescent cells including G0-arrested tissue culture cells and prophase I-arrested oocytes. Quiescent CENP-A incorporation involves the canonical CENP-A deposition machinery but displays distinct requirements from cell cycle-dependent deposition. We demonstrate that Plk1 is required specifically for G1 CENP-A deposition, whereas transcription promotes CENP-A incorporation in quiescent oocytes. Preventing CENP-A deposition during quiescence results in significantly reduced CENP-A levels and perturbs chromosome segregation following the resumption of cell division. In contrast to quiescent cells, terminally differentiated cells fail to maintain CENP-A levels. Our work reveals that quiescent cells actively maintain centromere identity providing an indicator of proliferative potential.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.devcel.2019.07.016
