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Genome research2018; 28(6); 789-799; doi: 10.1101/gr.231159.117

Birth, evolution, and transmission of satellite-free mammalian centromeric domains.

Abstract: Mammalian centromeres are associated with highly repetitive DNA (satellite DNA), which has so far hindered molecular analysis of this chromatin domain. Centromeres are epigenetically specified, and binding of the CENPA protein is their main determinant. In previous work, we described the first example of a natural satellite-free centromere on Chromosome 11. Here, we investigated the satellite-free centromeres of by using ChIP-seq with anti-CENPA antibodies. We identified an extraordinarily high number of centromeres lacking satellite DNA (16 of 31). All of them lay in LINE- and AT-rich regions. A subset of these centromeres is associated with DNA amplification. The location of CENPA binding domains can vary in different individuals, giving rise to epialleles. The analysis of epiallele transmission in hybrids (three mules and one hinny) showed that centromeric domains are inherited as Mendelian traits, but their position can slide in one generation. Conversely, centromere location is stable during mitotic propagation of cultured cells. Our results demonstrate that the presence of more than half of centromeres void of satellite DNA is compatible with genome stability and species survival. The presence of amplified DNA at some centromeres suggests that these arrays may represent an intermediate stage toward satellite DNA formation during evolution. The fact that CENPA binding domains can move within relatively restricted regions (a few hundred kilobases) suggests that the centromeric function is physically limited by epigenetic boundaries.
© 2018 Nergadze et al.; Published by Cold Spring Harbor Laboratory Press.
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Publication Date: 2018-04-30 PubMed ID: 29712753PubMed Central: PMC5991519DOI: 10.1101/gr.231159.117Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores the nature of mammalian centromeres, specifically the example of satellite-free centromeres in Chromosome 11. The researchers utilized ChIP-seq with anti-CENPA antibodies to examine these centromeres and found a surprising number of centromeres lacking satellite DNA. The analysis also suggests that the position of these centromeres can slightly differ between individuals and generations, but remains generally stable during cell division. The study advances our understanding of genome stability and the potential evolutionary path of these centromere types.

Exploration of Satellite-free Centromeres

  • The researchers use ChIP-seq, a method to analyze protein interactions with DNA, to investigate the centromeres of Chromosome 11. They utilize anti-CENPA antibodies, as CENPA protein is a crucial component in the formation of centromeres.
  • In the process, they found a remarkably high number of centromeres that have no satellite DNA, which is a kind of repetitive DNA commonly present in typical centromeres. Out of 31, 16 centromeres were found to be void of satellite DNA, laying specifically in regions rich in LINE and AT elements.

Variations and Inheritance of Centromeres

  • The study also discovered variations in the location of CENPA binding domains across different individuals, indicating the existence of epigenetic variations or ‘epialleles’. These variations aren’t changes in the genome itself, but modifications in the expression of the genes that can be passed on to the next generations.
  • By analyzing the transmission of these variations in hybrids (mules and a hinny), the researchers found that while these centromeric domains are inherited following Mendelian genetics rules, their physical position on the chromosome can change over a single generation. However, the location of the centromeres maintains stability during cell division.

Implications for Evolution and Genome Stability

  • The research concludes that over half of the centromeres being void of satellite DNA does not interfere with genetic stability or species survival. This challenges previous notions about the necessity of satellite DNA for proper centromere function and genome stability.
  • Moreover, the presence of amplified DNA sequences at some centromeres may serve as an intermediate stage in the evolution of satellite DNA. This offers a new perspective on the evolutionary path of centromeres.
  • The observation that CENPA binding domains can shift their position within specific regions hints that the centromeric function might be under the control of certain epigenetic boundaries. Hence, even though the genetic content of these centromeric regions can vary between individuals and generations, their function remains restricted within specific physical constraints.

Cite This Article

APA
(2018). Birth, evolution, and transmission of satellite-free mammalian centromeric domains. Genome Res, 28(6), 789-799. https://doi.org/10.1101/gr.231159.117

Publication

Genome research
ISSN: 1549-5469
NlmUniqueID: 9518021
Country: United States
Language: English
Volume: 28
Issue: 6
Pages: 789-799

Researcher Affiliations

MeSH Terms

  • Animals
  • Autoantigens / genetics
  • Centromere / genetics
  • Centromere Protein A / genetics
  • Chromatin / genetics
  • DNA, Satellite / genetics
  • Evolution, Molecular
  • Genomic Instability / genetics
  • Horses
  • Mammals

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