The quantitative architecture of centromeric chromatin.

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

doi:10.7554/elife.02137

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.

Highlights

Centromeres are essential for proper cell division
A transient structure called the kinetochore is assembled onto centromeric chromatin, which mediates the interaction between DNA and the mitotic spindle (Allshire and Karpen, 2008; Cheeseman and Desai, 2008)
It has been proposed that centromeres in budding yeast feature a single nucleosome of CENP-ACse4 (Meluh et al, 1998; Furuyama and Biggins, 2007)

Summary

Introduction

Centromeres are essential for proper cell division. During mitosis, a transient structure called the kinetochore is assembled onto centromeric chromatin, which mediates the interaction between DNA and the mitotic spindle (Allshire and Karpen, 2008; Cheeseman and Desai, 2008). CENP-A is stably transmitted at centromeres during mitotic (Jansen et al, 2007; Bodor et al, 2013) and meiotic (Raychaudhuri et al, 2012) divisions, and its assembly is tightly cell cycle controlled (Jansen et al, 2007; Schuh et al, 2007; Silva et al, 2012).

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