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CENP-A/CENP-B Uncoupling in the Evolutionary Reshuffling of Centromeres in Equids

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Journal Genome Biol
Date 2025 Feb 6
PMID 39915813
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Abstract

Background: 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.

Citing Articles

CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids.

Cappelletti E, Piras F, Biundo M, Raimondi E, Nergadze S, Giulotto E Genome Biol. 2025; 26(1):23.

PMID: 39915813 PMC: 11804003. DOI: 10.1186/s13059-025-03490-0.

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