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 ET Jansen
Affiliations
Dani L Bodor
Instituto Gulbenkian de Ciência, Oeiras, Portugal
João F Mata
Instituto Gulbenkian de Ciência, Oeiras, Portugal
Mikhail Sergeev
Department of Systems Biology, Harvard Medical School, Boston, United States; Renal Division, Brigham and Women's Hospital, Boston, United States
Ana Filipa David
Instituto Gulbenkian de Ciência, Oeiras, Portugal
Kevan J Salimian
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Tanya Panchenko
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Don W Cleveland
Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States
Ben E Black
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Jagesh V Shah
Department of Systems Biology, Harvard Medical School, Boston, United States; Renal Division, Brigham and Women's Hospital, Boston, United States
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.
