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Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres

BACKGROUND: Chromatin containing the histone variant CENP-A (CEN chromatin) exists as an essential domain at every centromere and heritably marks the location of kinetochore assembly. The size of the CEN chromatin domain on alpha satellite DNA in humans has been shown to vary according to underlying...

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Autores principales: Ross, Justyne E., Woodlief, Kaitlin Stimpson, Sullivan, Beth A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888493/
https://www.ncbi.nlm.nih.gov/pubmed/27252782
http://dx.doi.org/10.1186/s13072-016-0071-7
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author Ross, Justyne E.
Woodlief, Kaitlin Stimpson
Sullivan, Beth A.
author_facet Ross, Justyne E.
Woodlief, Kaitlin Stimpson
Sullivan, Beth A.
author_sort Ross, Justyne E.
collection PubMed
description BACKGROUND: Chromatin containing the histone variant CENP-A (CEN chromatin) exists as an essential domain at every centromere and heritably marks the location of kinetochore assembly. The size of the CEN chromatin domain on alpha satellite DNA in humans has been shown to vary according to underlying array size. However, the average amount of CENP-A reported at human centromeres is largely consistent, implying the genomic extent of CENP-A chromatin domains more likely reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes within individual subdomains. Defining the organizational and spatial properties of CEN chromatin would provide insight into centromere inheritance via CENP-A loading in G1 and the dynamics of its distribution between mother and daughter strands during replication. RESULTS: Using a multi-color protein strategy to detect distinct pools of CENP-A over several cell cycles, we show that nascent CENP-A is equally distributed to sister centromeres. CENP-A distribution is independent of previous or subsequent cell cycles in that centromeres showing disproportionately distributed CENP-A in one cycle can equally divide CENP-A nucleosomes in the next cycle. Furthermore, we show using extended chromatin fibers that maintenance of the CENP-A chromatin domain is achieved by a cycle-specific oscillating pattern of new CENP-A nucleosomes next to existing CENP-A nucleosomes over multiple cell cycles. Finally, we demonstrate that the size of the CENP-A domain does not change throughout the cell cycle and is spatially fixed to a similar location within a given alpha satellite DNA array. CONCLUSIONS: We demonstrate that most human chromosomes share similar patterns of CENP-A loading and distribution and that centromere inheritance is achieved through specific placement of new CENP-A near existing CENP-A as assembly occurs each cell cycle. The loading pattern fixes the location and size of the CENP-A domain on individual chromosomes. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere identity and genome stability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0071-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-48884932016-06-02 Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres Ross, Justyne E. Woodlief, Kaitlin Stimpson Sullivan, Beth A. Epigenetics Chromatin Research BACKGROUND: Chromatin containing the histone variant CENP-A (CEN chromatin) exists as an essential domain at every centromere and heritably marks the location of kinetochore assembly. The size of the CEN chromatin domain on alpha satellite DNA in humans has been shown to vary according to underlying array size. However, the average amount of CENP-A reported at human centromeres is largely consistent, implying the genomic extent of CENP-A chromatin domains more likely reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes within individual subdomains. Defining the organizational and spatial properties of CEN chromatin would provide insight into centromere inheritance via CENP-A loading in G1 and the dynamics of its distribution between mother and daughter strands during replication. RESULTS: Using a multi-color protein strategy to detect distinct pools of CENP-A over several cell cycles, we show that nascent CENP-A is equally distributed to sister centromeres. CENP-A distribution is independent of previous or subsequent cell cycles in that centromeres showing disproportionately distributed CENP-A in one cycle can equally divide CENP-A nucleosomes in the next cycle. Furthermore, we show using extended chromatin fibers that maintenance of the CENP-A chromatin domain is achieved by a cycle-specific oscillating pattern of new CENP-A nucleosomes next to existing CENP-A nucleosomes over multiple cell cycles. Finally, we demonstrate that the size of the CENP-A domain does not change throughout the cell cycle and is spatially fixed to a similar location within a given alpha satellite DNA array. CONCLUSIONS: We demonstrate that most human chromosomes share similar patterns of CENP-A loading and distribution and that centromere inheritance is achieved through specific placement of new CENP-A near existing CENP-A as assembly occurs each cell cycle. The loading pattern fixes the location and size of the CENP-A domain on individual chromosomes. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere identity and genome stability. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0071-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-31 /pmc/articles/PMC4888493/ /pubmed/27252782 http://dx.doi.org/10.1186/s13072-016-0071-7 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ross, Justyne E.
Woodlief, Kaitlin Stimpson
Sullivan, Beth A.
Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
title Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
title_full Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
title_fullStr Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
title_full_unstemmed Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
title_short Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
title_sort inheritance of the cenp-a chromatin domain is spatially and temporally constrained at human centromeres
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888493/
https://www.ncbi.nlm.nih.gov/pubmed/27252782
http://dx.doi.org/10.1186/s13072-016-0071-7
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