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Octameric CENP-A Nucleosomes Are Present at Human Centromeres throughout the Cell Cycle.

Padeganeh A, Ryan J, Boisvert J, Ladouceur AM, Dorn JF, Maddox PS

Institute for Research in Immunology and Cancer (IRIC), Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada; Graduate programs in Molecular Biology-Systems Biology Option, Faculty of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada.

The presence of a single centromere on each chromosome that signals formation of a mitotic kinetochore is central to accurate chromosome segregation [1]. The histone H3 variant centromere protein-A (CENP-A) is critical for centromere identity and function; CENP-A chromatin acts as an epigenetic mark to direct both centromere and kinetochore assembly [2-4]. Interpreting the centromere epigenetic mark ensures propagation of a single centromere per chromosome to maintain ploidy. Thus, understanding the nature of CENP-A chromatin is crucial for all cell divisions. However, there are ongoing debates over the fundamental composition of centromeric chromatin. Here we show that natively assembled human CENP-A nucleosomes are octameric throughout the cell cycle. Using total internal reflection fluorescence (TIRF)-coupled photobleaching-assisted copy-number counting of single nucleosomes obtained from cultured cells, we find that the majority of CENP-A nucleosomes contain CENP-A dimers. In addition, we detect the presence of H2B and H4 in these nucleosomes. Surprisingly, CENP-A associated with the chaperone HJURP can exist as either monomer or dimer, indicating possible assembly intermediates. Thus, our findings indicate that octameric CENP-A nucleosomes mark the centromeric region to ensure proper epigenetic inheritance and kinetochore assembly.

Curr. Biol. 2013;23(9):764-9.

Pubmed ID: 23623556

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