Quiescent Cells Actively Replenish CENP-A Nucleosomes to Maintain Centromere Identity and Proliferative Potential

Dev Cell. 2019 Oct 7;51(1):35-48.e7. doi: 10.1016/j.devcel.2019.07.016. Epub 2019 Aug 15.


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.

Keywords: cell division; centromere; epigenetics; kinetochore; meiosis; mitosis; oocyte; quiescence; terminal differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cell Proliferation
  • Centromere / metabolism*
  • Centromere / ultrastructure
  • Centromere Protein A / metabolism*
  • Epigenesis, Genetic
  • Female
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Male
  • Meiosis
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / metabolism*
  • Nucleosomes / metabolism*
  • Oocytes / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • RNA, Small Interfering / metabolism
  • Starfish / metabolism
  • Testis / metabolism


  • Cell Cycle Proteins
  • Centromere Protein A
  • Nucleosomes
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Green Fluorescent Proteins
  • Protein Serine-Threonine Kinases
  • polo-like kinase 1