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

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 rep...

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Main Authors: Eleonora Cappelletti, Francesca M. Piras, Marialaura Biundo, Elena Raimondi, Solomon G. Nergadze, Elena Giulotto
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Genome Biology
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Online Access:https://doi.org/10.1186/s13059-025-03490-0
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author Eleonora Cappelletti
Francesca M. Piras
Marialaura Biundo
Elena Raimondi
Solomon G. Nergadze
Elena Giulotto
author_facet Eleonora Cappelletti
Francesca M. Piras
Marialaura Biundo
Elena Raimondi
Solomon G. Nergadze
Elena Giulotto
author_sort Eleonora Cappelletti
collection DOAJ
description 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.
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spelling doaj-art-fb66a429b37843fcba3c17f12cdabe8d2025-02-09T12:39:24ZengBMCGenome Biology1474-760X2025-02-0126113110.1186/s13059-025-03490-0CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equidsEleonora Cappelletti0Francesca M. Piras1Marialaura Biundo2Elena Raimondi3Solomon G. Nergadze4Elena Giulotto5Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of PaviaUnit of Anatomic Pathology, IRCCS San Matteo Hospital FoundationDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of PaviaDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of PaviaDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of PaviaDepartment of Biology and Biotechnology “Lazzaro Spallanzani”, University of PaviaAbstract 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.https://doi.org/10.1186/s13059-025-03490-0CENP-BCentromereSatellite DNAKaryotype evolutionGenus Equus
spellingShingle Eleonora Cappelletti
Francesca M. Piras
Marialaura Biundo
Elena Raimondi
Solomon G. Nergadze
Elena Giulotto
CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids
Genome Biology
CENP-B
Centromere
Satellite DNA
Karyotype evolution
Genus Equus
title CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids
title_full CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids
title_fullStr CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids
title_full_unstemmed CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids
title_short CENP-A/CENP-B uncoupling in the evolutionary reshuffling of centromeres in equids
title_sort cenp a cenp b uncoupling in the evolutionary reshuffling of centromeres in equids
topic CENP-B
Centromere
Satellite DNA
Karyotype evolution
Genus Equus
url https://doi.org/10.1186/s13059-025-03490-0
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