The octamer is the major form of CENP-A nucleosomes at human centromeres

Hasson, Dan; Panchenko, Tanya; Salimian, Kevan J.; Salman, Mishah Uzziel; Sekulić, Nikolina; Alonso, Alicia; Warburton, Peter E.; Black, Ben E.

doi:10.1038/nsmb.2562

Cited by 206 publications

(311 citation statements)

References 51 publications

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“…A final feature of the analysis was a 10-bp periodicity of CentO, one turn of the DNA double helix A 10bp rotational phasing minimizes the bending energy or strain on the folded DNA and increases stability. The unexpected 100-bp result in rice has now also been found in human cells (13) where the CENP-A (CenH3) nucleosome protects only 110 bp of the 171-bp-long α-satellite from MNase digestion. Could there be an alternative packaging structure involving CENH3?…”

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confidence: 92%

Nucleosomes and centromeric DNA packaging

Heslop-Harrison

Schwarzacher

2013

Proc. Natl. Acad. Sci. U.S.A.

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The eukaryotic chromosome is a conserved structure, with the DNA double-helix wrapping around octamers of histone proteins to form the chromatin, which is further packaged into chromosomes. The centromere defines the kinetochore, the region of spindle microtubule attachment that pulls the two replicated chromatids of each chromosome apart during cell division (Fig. 1), leading to fidelity in transmission of genetic information. Like the telomere, centromeres are well defined morphologically and functionally, but their DNA sequence shows no conservation between species, and their coiling into chromatin is still poorly understood. In PNAS, Zhang et al. (1) give unique insight into the centromeric CenH3-nucleosomes associated with the rice CentO satellite sequence and adjacent regions of DNA, having implications for centromere specification, activity, and evolution.Centromeres are readily observed as partial constrictions on the metaphase chromosome by light or electron microscopy ( Fig. 1). However, few sequence-related characteristics of the DNA at the centromeres are conserved. In contrast, nucleosome proteins (2) and kinetochores linking centromeres and spindle microtubules with a multiprotein complex are highly conserved across all kingdoms (3).Typically, there are tandemly repeated satellite DNA sequences at the centromeres of chromosomes of animals and plants (4-6). Detailed work on the budding yeast Schizosaccharomyces pombe and brewer's yeast Saccharomyces cerevisiae identified relatively short DNA sequences and binding protein counterparts that direct chromosome segregation (7,8). The search was then on for critical "boxes" in plants and animals but, although some motifs were found to be involved in protein-DNA interactions, no motif shared across diverse phyla was found within the centromeric tandem repeats.As sequencing technology advanced, both variants of tandem repeats and almost any other class of DNA-retrotransposons, transposons, genes, transcription factors, and microsatellites-were revealed (9) underlying the kinetochore and microtubule attachment sites. Evidence from comparisons of species, mutants that still showed centromeric function, the lack of necessity for tandemly repeated satellite sequence, and the presence of (1) with ∼100 bp of the rice CentO tandem repeat sequence (red) folding once around the nucleosome core that includes CenH3 (yellow). (I) A key method for nucleosome analysis involving micrococcal nuclease digestion of chromatin and size separation of the resultant DNA fragments; the enzyme cuts DNA in the linker regions and, over the time course shown, isolates more mononucleosomes, and trims overhanging DNA not protected from digestion by the histone proteins (12). (Scale bars for A-C, 2 μm.)

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confidence: 92%

Nucleosomes and centromeric DNA packaging

Heslop-Harrison

Schwarzacher

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, a new centromeric repeat can sweep through the entire genome and rapidly replace the old repeat in all centromeres via poorly understood mechanisms. The cenH3/CENP-A nucleosomes in rice and humans are highly phased on the 155/ 171-bp monomers of the CentO and alpha satellite repeats, respectively, and show a distinct structure compared to canonical nucleosomes (Hasson et al 2013;Zhang et al 2013b). Therefore, satellite repeats are intrinsically more suitable for organizing centromeric nucleosomes than single-and lowcopy DNA sequences.…”

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Three Potato Centromeres Are Associated with Distinct Haplotypes with or Without Megabase-Sized Satellite Repeat Arrays

et al. 2014

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“…In human cultured cells, substantial translational phasing of CENP-A, the human cenH3, was reported on α-satellite (20). In maize, a similar approach mapped CENH3 (the name used for plant cenH3s) on the 156-bp maize centromeric satellite CentC and on two retrotransposon-derived centromeric sequences, CRM1 and CRM2 (21).…”

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The CentO satellite confers translational and rotational phasing on cenH3 nucleosomes in rice centromeres

Zhang

Talbert

Zhang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Plant and animal centromeres comprise megabases of highly repeated satellite sequences, yet centromere function can be specified epigenetically on single-copy DNA by the presence of nucleosomes containing a centromere-specific variant of histone H3 (cenH3). We determined the positions of cenH3 nucleosomes in rice (Oryza sativa), which has centromeres composed of both the 155-bp CentO satellite repeat and single-copy non-CentO sequences. We find that cenH3 nucleosomes protect 90-100 bp of DNA from micrococcal nuclease digestion, sufficient for only a single wrap of DNA around the cenH3 nucleosome core. cenH3 nucleosomes are translationally phased with 155-bp periodicity on CentO repeats, but not on non-CentO sequences. CentO repeats have an ∼10-bp periodicity in WW dinucleotides and in micrococcal nuclease cleavage, providing evidence for rotational phasing of cenH3 nucleosomes on CentO and suggesting that satellites evolve for translational and rotational stabilization of centromeric nucleosomes.CENP-A | nucleosome phasing | epigenetics | kinetochore C entromeres, the chromosomal domains that attach to spindle microtubules to segregate eukaryotic chromosomes in mitosis and meiosis, are DNA elements bound by special nucleosomes that contain a centromere-specific variant of histone H3 (cenH3). In most plants and animals, cenH3 nucleosomes are found on centromeric DNA that comprises megabases of tandemly repeated "satellite" sequences. Despite this apparent preference for repetitive DNA, a fully functional centromere, called a neocentromere, can occasionally form by assembling cenH3 nucleosomes on a single-copy DNA sequence that was not previously part of a centromere, indicating that centromere specification is epigenetic in plants and animals (for reviews, see refs. 1-4).The tandem arrays of highly repeated satellite sequences that compose most plant and animal centromeres can differ dramatically between closely related species (5), and even between different chromosomes (6-8), suggesting that satellite arrays undergo rapid evolution through expansions, contractions, gene conversions, and transpositions. Monomers of satellite repeats range in length from 5 bp in Drosophila to 1,419 bp in cattle although more than half of described monomers in 282 species have lengths between 100 and 200 bp, often regarded as approximately the length of nucleosomal DNA (6, 9). The cenH3 nucleosomes typically occupy only a portion of the satellite repeats, often in discontinuous blocks (7, 10-12), and the same or similar repeats often underlie flanking pericentromeric heterochromatin composed of conventional nucleosomes. Some of these repeats, for example African green monkey α-satellite DNA, have long been known to position conventional nucleosomes, resulting in arrays of regularly spaced nucleosomes, said to be translationally phased (13-15). Nucleosomes can occupy multiple alternative translational phases on the same satellite (16, 17). Translationally phased nucleosomal arrays have also been observed on satellites in cucumber a...

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The octamer is the major form of CENP-A nucleosomes at human centromeres

Cited by 206 publications

References 51 publications

Nucleosomes and centromeric DNA packaging

Nucleosomes and centromeric DNA packaging

Three Potato Centromeres Are Associated with Distinct Haplotypes with or Without Megabase-Sized Satellite Repeat Arrays

The CentO satellite confers translational and rotational phasing on cenH3 nucleosomes in rice centromeres

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