The quantitative architecture of centromeric chromatin

• Published in: eLife Vol. 3; p. e02137
• Main Authors: Bodor, Dani L, Mata, João F, Sergeev, Mikhail, David, Ana Filipa, Salimian, Kevan J, Panchenko, Tanya, Cleveland, Don W, Black, Ben E, Shah, Jagesh V, Jansen, Lars Et
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 15.07.2014; eLife Sciences Publications, Ltd
• Subjects: Alleles; Autoantigens - genetics; Autoantigens - metabolism; Binomial distribution; Cell Biology; Cell cycle; Cell division; CENP-A; Centromere; Centromere Protein A; Centromeres; Chromatin; Chromatin - chemistry; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Diploidy; epigenetic; Epigenetics; Experiments; Gene Dosage; Genomes; Heredity; histone variant; Humans; Mitosis; molecular counting; Nucleosomes; Proteins; quantitative microscopy; Stochastic Processes; Stochasticity; California; quantitative microscopy; histone variant; centromere; CENP-A; molecular counting; epigenetics
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.02137

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.