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      Anarchic centromeres: deciphering order from apparent chaos ☆

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      Publication date PMC-release:
      Journal: Current Opinion in Cell Biology
      Publisher: Elsevier

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          Abstract

          Specialised chromatin in which canonical histone H3 is replaced by CENP-A, an H3 related protein, is a signature of active centromeres and provides the foundation for kinetochore assembly. The location of centromeres is not fixed since centromeres can be inactivated and new centromeres can arise at novel locations independently of specific DNA sequence elements. Therefore, the establishment and maintenance of CENP-A chromatin and kinetochores provide an exquisite example of genuine epigenetic regulation. The composition of CENP-A nucleosomes is contentious but several studies suggest that, like regular H3 particles, they are octamers. Recent analyses have provided insight into how CENP-A is recognised and propagated, identified roles for post-translational modifications and dissected how CENP-A recruits other centromere proteins to mediate kinetochore assembly.

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          Genome sequence, comparative analysis, and population genetics of the domestic horse.

          C. Wade, E Giulotto, S Sigurdsson … (2009)
          We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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            Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore.

            Emily A Foley, Tarun Kapoor (2013)
            In eukaryotes, chromosome segregation during cell division is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric DNA. The kinetochore attaches chromosomes to spindle microtubules, modulates the stability of these attachments and relays the microtubule-binding status to the spindle assembly checkpoint (SAC), a cell cycle surveillance pathway that delays chromosome segregation in response to unattached kinetochores. Recent studies are shaping current thinking on how each of these kinetochore-centred processes is achieved, and how their integration ensures faithful chromosome segregation, focusing on the essential roles of kinase-phosphatase signalling and the microtubule-binding KMN protein network.
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              Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP.

              Daniel Foltz, Lars Jansen, Aaron Bailey … (2009)
              The centromere is responsible for accurate chromosome segregation. Mammalian centromeres are specified epigenetically, with all active centromeres containing centromere-specific chromatin in which CENP-A replaces histone H3 within the nucleosome. The proteins responsible for assembly of human CENP-A into centromeric nucleosomes during the G1 phase of the cell cycle are shown here to be distinct from the chromatin assembly factors previously shown to load other histone H3 variants. Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.
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                Author and article information

                Contributors
                Robin C Allshire
                Journal
                Journal ID (nlm-ta): Curr Opin Cell Biol
                Journal ID (iso-abbrev): Curr. Opin. Cell Biol
                Title: Current Opinion in Cell Biology
                Publisher: Elsevier
                ISSN (Print): 0955-0674
                ISSN (Electronic): 1879-0410
                Publication date PMC-release: 1 February 2014
                Publication date (Print): February 2014
                Volume: 26
                Issue: 100
                Pages: 41-50
                Affiliations
                [0005]Wellcome Trust Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, 6.34 Swann Building, Mayfield Road, Edinburgh EH9 3JR, Scotland, UK
                Article
                Publisher ID: S0955-0674(13)00152-X
                DOI: 10.1016/j.ceb.2013.09.004
                PMC ID: 3978670
                PubMed ID: 24529245
                SO-VID: d0ce53c1-35ae-4516-9b15-6a2c0c71b98e
                Copyright © © 2013 The Authors
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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                ScienceOpen disciplines: Cell biology
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                ScienceOpen disciplines: Cell biology

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