title: The quantitative architecture of centromeric chromatin.
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.DOI: http://dx.doi.org/10.7554/eLife.02137.001.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Dani L
authors.initials: DL
authors.lastname: Bodor
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: João F
authors.initials: JF
authors.lastname: Mata
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, United States Renal Division, Brigham and Women's Hospital, Boston, United States.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Sergeev
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: David
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
authors.forename: Kevan J
authors.initials: KJ
authors.lastname: Salimian
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
authors.forename: Tanya
authors.initials: T
authors.lastname: Panchenko
authors.affiliation: 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.
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, United States Renal Division, Brigham and Women's Hospital, Boston, United States.
authors.forename: Jagesh V
authors.initials: JV
authors.lastname: Shah
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal ljansen@igc.gulbenkian.pt.
authors.forename: Lars Et
authors.initials: LE
authors.lastname: Jansen
mesh_terms: D000483:Alleles; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002503:Centromere; D000076247:Centromere Protein A; D002843:Chromatin / Q000737:chemistry*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004171:Diploidy; D018628:Gene Dosage; D006801:Humans; D013269:Stochastic Processes
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone
keywords: CENP-A; centromere; epigenetics; histone variant; molecular counting; quantitative microscopy