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bioRxiv · 10.1101/433391

Quiescent cells actively replenish CENP-A nucleosomes to maintain centromere identity and proliferative potential

Swartz, S. Z.·McKay, L. S.·Su, K.-C.·Padeganeh, A.·Maddox, P. S.·Knouse, K. A.·Cheeseman, I.
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Abstract

Centromeres provide a robust model for epigenetic inheritance as they are specified by sequence-independent mechanisms involving the histone H3-variant 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.

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Swartz, S. Z., McKay, L. S., Su, K.-C., Padeganeh, A., Maddox, P. S., Knouse, K. A., Cheeseman, I.. 2018-10-02. Quiescent cells actively replenish CENP-A nucleosomes to maintain centromere identity and proliferative potential. https://doi.org/10.1101/433391

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