Dataset Information

Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control.

ABSTRACT: Chromosome segregation during cell division is driven by mitotic spindle attachment to the centromere region on each chromosome. Centromeres form a protein scaffold defined by chromatin featuring CENP-A, a conserved histone H3 variant, in a manner largely independent of local DNA cis elements. CENP-A nucleosomes fulfill two essential criteria to epigenetically identify the centromere. They undergo self-templated duplication to reestablish centromeric chromatin following DNA replication. More importantly, CENP-A incorporated into centromeric chromatin is stably transmitted through consecutive cell division cycles. CENP-A nucleosomes have unique structural properties and binding partners that potentially explain their long lifetime in vivo. However, rather than a static building block, centromeric chromatin is dynamically regulated throughout the cell cycle, indicating that CENP-A stability is also controlled by external factors. We discuss recent insights and identify the outstanding questions on how dynamic control of the long-term stability of CENP-A ensures epigenetic centromere inheritance.

SUBMITTER: Mitra S

PROVIDER: S-EPMC7659725 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control.

Mitra Sreyoshi S Srinivasan Bharath B Jansen Lars E T LET

The Journal of cell biology 20201001 10

Chromosome segregation during cell division is driven by mitotic spindle attachment to the centromere region on each chromosome. Centromeres form a protein scaffold defined by chromatin featuring CENP-A, a conserved histone H3 variant, in a manner largely independent of local DNA cis elements. CENP-A nucleosomes fulfill two essential criteria to epigenetically identify the centromere. They undergo self-templated duplication to reestablish centromeric chromatin following DNA replication. More imp ...[more]

PMID: 32931551

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Project description:BackgroundChromatin 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.ResultsUsing 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.ConclusionsWe 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.

Dataset Information

Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control.

Publications

Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control.

Similar Datasets

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