Journal
ELIFE
Volume 3, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.02137
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Funding
- European Molecular Biology Organization EMBO Installation grant
- European Commission
- European Research Council [ERC-2013-CoG-615638]
- National Institutes of Health [GM082989, GM077238]
- Burroughs Wellcome Fund
- Rita Allen Foundation
- Beckman Laser Institute and Foundation
- Fundacao para a Ciencia e a Tecnologia (Foundation for Science and Technology) [SFRH/BD/74284/2010, BIA-BCM/100557/2008, BIA-PRO/100537/2008]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/74284/2010, PTDC/BIA-BCM/100557/2008, PTDC/BIA-PRO/100537/2008] Funding Source: FCT
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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 similar to 400 molecules of CENP-A, which is controlled by a mass-action mechanism. This number, despite representing only similar to 4% of all centromeric nucleosomes, forms a similar to 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.
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