The quantitative architecture of centromeric chromatin

Dani L. Bodor, João F. Mata, Mikhail Sergeev, Ana Filipa David, Kevan J. Salimian, Tanya Panchenko, Don W. Cleveland, Ben E. Black, Jagesh V. Shah, Lars E.T. Jansen

Research output: Contribution to journalArticlepeer-review

Abstract

The centromere, responsible for chromosome segregation during mitosis, is epigenetically defined by CENP-A containing chromatin. The amount of centromeric CENP-A has direct implications for both the architecture and epigenetic inheritance of centromeres. Using complementary strategies, we determined that typical human centromeres contain ~400 molecules of CENP-A, which is controlled by a mass-action mechanism. This number, despite representing only ~4% of all centromeric nucleosomes, forms a ~50-fold enrichment to the overall genome. In addition, although pre-assembled CENP-A is randomly segregated during cell division, this amount of CENP-A is sufficient to prevent stochastic loss of centromere function and identity. Finally, we produced a statistical map of CENP-A occupancy at a human neocentromere and identified nucleosome positions that feature CENP-A in a majority of cells. In summary, we present a quantitative view of the centromere that provides a mechanistic framework for both robust epigenetic inheritance of centromeres and the paucity of neocentromere formation.

Original languageEnglish (US)
Article numbere02137
JournaleLife
Volume2014
Issue number3
DOIs
StatePublished - Jul 15 2014

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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