CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids.
Abstract: While CENP-A is the epigenetic determinant of the centromeric function, the role of CENP-B, a centromeric protein binding a specific DNA sequence, the CENP-B-box, remains elusive. In the few mammalian species analyzed so far, the CENP-B box is contained in the major satellite repeat that is present at all centromeres, with the exception of the Y chromosome. We previously demonstrated that, in the genus Equus, numerous centromeres lack any satellite repeat. Results: In four Equus species, CENP-B is expressed but does not bind the majority of satellite-based centromeres, or the satellite-free ones, while it is localized at several ancestral, now-inactive, centromeres. Centromeres lacking CENP-B are functional and recruit normal amounts of CENP-A and CENP-C. The absence of CENP-B is related to the lack of CENP-B boxes rather than to peculiar features of the protein itself. CENP-B boxes are present in a previously undescribed repeat which is not the major satellite bound by CENP-A. Comparative sequence analysis suggests that this satellite was centromeric in the equid ancestor, lost centromeric function during evolution, and gave rise to a shorter CENP-A bound repeat not containing the CENP-B box but enriched in dyad symmetries. Conclusions: We propose that the uncoupling between CENP-B and CENP-A may have played a role in the extensive evolutionary reshuffling of equid centromeres. This study provides new insights into the complexity of centromere organization in a largely biodiverse world where the majority of mammalian species still have to be studied.
© 2025. The Author(s).
Publication Date: 2025-02-06 PubMed ID: 39915813PubMed Central: PMC11804003DOI: 10.1186/s13059-025-03490-0Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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CENP-A and CENP-B are proteins involved in the function and structure of centromeres, the chromosome regions critical for cell division. This study investigates how these proteins interact with centromeric DNA in different horse species, revealing that CENP-B does not always associate with centromeres, suggesting a unique evolutionary pathway for centromere organization in equids.
Background and Research Motivation
- Centromeres are essential chromosomal regions acting as anchors during cell division, ensuring proper chromosome segregation.
- CENP-A is a protein recognized as the key epigenetic marker defining centromere identity and function.
- CENP-B is another centromeric protein that binds specifically to a DNA sequence known as the CENP-B box, often found in satellite DNA repeats at centromeres.
- Previous studies in mammals show that the CENP-B box is present in major satellite repeats at almost all centromeres, except on the Y chromosome.
- The genus Equus, which includes horses and related species, is unique because many of their centromeres lack traditional satellite DNA repeats.
- The study aims to explore the relationship between CENP-A and CENP-B proteins and their DNA-binding sites in equids to understand centromere evolution and organization.
Key Findings
- CENP-B protein is expressed in four different Equus species (horse family members).
- Despite its presence, CENP-B does not bind to most centromeres that contain satellite DNA nor to those lacking satellite DNA.
- CENP-B localizes instead to several ancestral centromeres which are currently inactive (no longer serving a centromeric function).
- Centromeres without CENP-B are still fully functional, recruiting normal levels of CENP-A and CENP-C proteins, both important for centromere activity.
- The lack of CENP-B binding corresponds to an absence of the CENP-B box DNA sequence, not to any unusual features in the CENP-B protein itself.
- A previously undescribed DNA repeat containing CENP-B boxes was discovered, but this repeat is not the major satellite sequence that binds CENP-A.
- Comparative sequence analyses suggest this satellite DNA was centromeric in the equid ancestor but lost its centromere function over time, evolving into a shorter repeat sequence lacking the CENP-B box but rich in dyad symmetries (a particular DNA structure).
Conclusions and Implications
- The decoupling or “uncoupling” of CENP-B and CENP-A binding activities may have been an important factor in the extensive evolutionary rearrangement of centromeres observed in equids.
- This uncoupling challenges the previously assumed strict link between satellite DNA, CENP-B presence, and centromere function in mammals.
- Centromeres can remain functional without CENP-B, indicating variability in centromere organization and suggesting alternative mechanisms ensuring centromere stability and inheritance.
- The findings highlight the complexity and diversity of centromere structures in natural populations and underscore the importance of studying more species beyond traditional mammalian models.
- This research contributes to the broader understanding of chromosome evolution and epigenetic regulation in diverse taxa, helping explain how centromeres can adapt and evolve across species.
Cite This Article
APA
(2025).
CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids.
Genome Biol, 26(1), 23.
https://doi.org/10.1186/s13059-025-03490-0 Publication
Researcher Affiliations
MeSH Terms
- Centromere / genetics
- Centromere / metabolism
- Animals
- Centromere Protein A
- Centromere Protein B / genetics
- Centromere Protein B / metabolism
- Evolution, Molecular
- Equidae / genetics
- DNA, Satellite / genetics
- Autoantigens / genetics
- Autoantigens / metabolism
- Chromosomal Proteins, Non-Histone / genetics
- Chromosomal Proteins, Non-Histone / metabolism
- Horses / genetics
Grant Funding
- 2019-67015-29340 / National Institute of Food and Agriculture
Conflict of Interest Statement
Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.
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Citations
This article has been cited 5 times.- Giunta S, Fukagawa T, O'Neill RJ, Akiyoshi B. 40 years of CENP-A: the foundation of a new era of centromere biology.. Chromosoma 2025 Dec 22;134(1):13.
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