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19 pages, 2331 KiB

Open AccessReview

Flexible Attachment and Detachment of Centromeres and Telomeres to and from Chromosomes

by Riku Kuse and Kojiro Ishii

Biomolecules 2023, 13(6), 1016; https://doi.org/10.3390/biom13061016 - 20 Jun 2023

Viewed by 2496

Accurate transmission of genomic information across multiple cell divisions and generations, without any losses or errors, is fundamental to all living organisms. To achieve this goal, eukaryotes devised chromosomes. Eukaryotic genomes are represented by multiple linear chromosomes in the nucleus, each carrying a centromere in the middle, a telomere at both ends, and multiple origins of replication along the chromosome arms. Although all three of these DNA elements are indispensable for chromosome function, centromeres and telomeres possess the potential to detach from the original chromosome and attach to new chromosomal positions, as evident from the events of telomere fusion, centromere inactivation, telomere healing, and neocentromere formation. These events seem to occur spontaneously in nature but have not yet been elucidated clearly, because they are relatively infrequent and sometimes detrimental. To address this issue, experimental setups have been developed using model organisms such as yeast. In this article, we review some of the key experiments that provide clues as to the extent to which these paradoxical and elusive features of chromosomally indispensable elements may become valuable in the natural context. Full article

(This article belongs to the Special Issue Yeast Models for Gene Regulation)

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16 pages, 1541 KiB

Open AccessArticle

A Satellite-Free Centromere in Equus przewalskii Chromosome 10

by Francesca M. Piras, Eleonora Cappelletti, Wasma A. Abdelgadir, Giulio Salamon, Simone Vignati, Marco Santagostino, Lorenzo Sola, Solomon G. Nergadze and Elena Giulotto

Int. J. Mol. Sci. 2023, 24(4), 4134; https://doi.org/10.3390/ijms24044134 - 18 Feb 2023

Cited by 5 | Viewed by 2897

Abstract

In mammals, centromeres are epigenetically specified by the histone H3 variant CENP-A and are typically associated with satellite DNA. We previously described the first example of a natural satellite-free centromere on Equus caballus chromosome 11 (ECA11) and, subsequently, on several chromosomes in other species of the genus Equus. We discovered that these satellite-free neocentromeres arose recently during evolution through centromere repositioning and/or chromosomal fusion, after inactivation of the ancestral centromere, where, in many cases, blocks of satellite sequences were maintained. Here, we investigated by FISH the chromosomal distribution of satellite DNA families in Equus przewalskii (EPR), demonstrating a good degree of conservation of the localization of the major horse satellite families 37cen and 2PI with the domestic horse. Moreover, we demonstrated, by ChIP-seq, that 37cen is the satellite bound by CENP-A and that the centromere of EPR10, the ortholog of ECA11, is devoid of satellite sequences. Our results confirm that these two species are closely related and that the event of centromere repositioning which gave rise to EPR10/ECA11 centromeres occurred in the common ancestor, before the separation of the two horse lineages. Full article

(This article belongs to the Special Issue Animal Genomes and Epigenomes)

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16 pages, 1340 KiB

Open AccessReview

Molecular Dynamics and Evolution of Centromeres in the Genus Equus

by Francesca M. Piras, Eleonora Cappelletti, Marco Santagostino, Solomon G. Nergadze, Elena Giulotto and Elena Raimondi

Int. J. Mol. Sci. 2022, 23(8), 4183; https://doi.org/10.3390/ijms23084183 - 10 Apr 2022

Cited by 9 | Viewed by 3777

Abstract

The centromere is the chromosomal locus essential for proper chromosome segregation. While the centromeric function is well conserved and epigenetically specified, centromeric DNA sequences are typically composed of satellite DNA and represent the most rapidly evolving sequences in eukaryotic genomes. The presence of satellite sequences at centromeres hampered the comprehensive molecular analysis of these enigmatic loci. The discovery of functional centromeres completely devoid of satellite repetitions and fixed in some animal and plant species represented a turning point in centromere biology, definitively proving the epigenetic nature of the centromere. The first satellite-free centromere, fixed in a vertebrate species, was discovered in the horse. Later, an extraordinary number of satellite-free neocentromeres had been discovered in other species of the genus Equus, which remains the only mammalian genus with numerous satellite-free centromeres described thus far. These neocentromeres arose recently during evolution and are caught in a stage of incomplete maturation. Their presence made the equids a unique model for investigating, at molecular level, the minimal requirements for centromere seeding and evolution. This model system provided new insights on how centromeres are established and transmitted to the progeny and on the role of satellite DNA in different aspects of centromere biology. Full article

(This article belongs to the Collection Feature Papers in “Molecular Biology”)

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22 pages, 2534 KiB

Open AccessReview

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

by Laura Leo and Nunzia Colonna Romano

Int. J. Mol. Sci. 2021, 22(16), 8809; https://doi.org/10.3390/ijms22168809 - 16 Aug 2021

Cited by 8 | Viewed by 5377

Abstract

Epigenetic regulators play a crucial role in establishing and maintaining gene expression states. To date, the main efforts to study cellular heterogeneity have focused on elucidating the variable nature of the chromatin landscape. Specific chromatin organisation is fundamental for normal organogenesis and developmental homeostasis and can be affected by different environmental factors. The latter can lead to detrimental alterations in gene transcription, as well as pathological conditions such as cancer. Epigenetic marks regulate the transcriptional output of cells. Centromeres are chromosome structures that are epigenetically regulated and are crucial for accurate segregation. The advent of single-cell epigenetic profiling has provided finer analytical resolution, exposing the intrinsic peculiarities of different cells within an apparently homogenous population. In this review, we discuss recent advances in methodologies applied to epigenetics, such as CUT&RUN and CUT&TAG. Then, we compare standard and emerging single-cell techniques and their relevance for investigating human diseases. Finally, we describe emerging methodologies that investigate centromeric chromatin specification and neocentromere formation. Full article

(This article belongs to the Special Issue Epigenetic Bioengineering)

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28 pages, 1816 KiB

Open AccessReview

Centromeres under Pressure: Evolutionary Innovation in Conflict with Conserved Function

by Elisa Balzano and Simona Giunta

Genes 2020, 11(8), 912; https://doi.org/10.3390/genes11080912 - 10 Aug 2020

Cited by 32 | Viewed by 5997

Abstract

Centromeres are essential genetic elements that enable spindle microtubule attachment for chromosome segregation during mitosis and meiosis. While this function is preserved across species, centromeres display an array of dynamic features, including: (1) rapidly evolving DNA; (2) wide evolutionary diversity in size, shape and organization; (3) evidence of mutational processes to generate homogenized repetitive arrays that characterize centromeres in several species; (4) tolerance to changes in position, as in the case of neocentromeres; and (5) intrinsic fragility derived by sequence composition and secondary DNA structures. Centromere drive underlies rapid centromere DNA evolution due to the “selfish” pursuit to bias meiotic transmission and promote the propagation of stronger centromeres. Yet, the origins of other dynamic features of centromeres remain unclear. Here, we review our current understanding of centromere evolution and plasticity. We also detail the mutagenic processes proposed to shape the divergent genetic nature of centromeres. Changes to centromeres are not simply evolutionary relics, but ongoing shifts that on one side promote centromere flexibility, but on the other can undermine centromere integrity and function with potential pathological implications such as genome instability. Full article

(This article belongs to the Special Issue The Role of Centromeres in Genome Stability)

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19 pages, 2592 KiB

Open AccessReview

Epigenetics as an Evolutionary Tool for Centromere Flexibility

by Laura Leo, Marcella Marchetti, Simona Giunta and Laura Fanti

Genes 2020, 11(7), 809; https://doi.org/10.3390/genes11070809 - 16 Jul 2020

Cited by 10 | Viewed by 4855

Abstract

Centromeres are the complex structures responsible for the proper segregation of chromosomes during cell division. Structural or functional alterations of the centromere cause aneuploidies and other chromosomal aberrations that can induce cell death with consequences on health and survival of the organism as a whole. Because of their essential function in the cell, centromeres have evolved high flexibility and mechanisms of tolerance to preserve their function following stress, whether it is originating from within or outside the cell. Here, we review the main epigenetic mechanisms of centromeres’ adaptability to preserve their functional stability, with particular reference to neocentromeres and holocentromeres. The centromere position can shift in response to altered chromosome structures, but how and why neocentromeres appear in a given chromosome region are still open questions. Models of neocentromere formation developed during the last few years will be hereby discussed. Moreover, we will discuss the evolutionary significance of diffuse centromeres (holocentromeres) in organisms such as nematodes. Despite the differences in DNA sequences, protein composition and centromere size, all of these diverse centromere structures promote efficient chromosome segregation, balancing genome stability and adaptability, and ensuring faithful genome inheritance at each cellular generation. Full article

(This article belongs to the Special Issue The Role of Centromeres in Genome Stability)

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5 pages, 343 KiB

Open AccessFeature PaperCommentary

CENP-A Ubiquitylation Contributes to Maintaining the Chromosomal Location of the Centromere

by Yohei Niikura, Risa Kitagawa and Katsumi Kitagawa

Molecules 2019, 24(3), 402; https://doi.org/10.3390/molecules24030402 - 22 Jan 2019

Cited by 9 | Viewed by 4803

Abstract

The centromere plays an essential role in accurate chromosome segregation, and the chromosomal location of the centromere is determined by the presence of a histone H3 variant, centromere protein A (CENP-A), in centromeric nucleosomes. However, the precise mechanisms of deposition, maintenance, and inheritance of CENP-A at centromeres are unclear. We have reported that CENP-A deposition requires ubiquitylation of CENP-A lysine 124 mediated by the E3 ligase activity of Cullin 4A (CUL4A)—RING-box protein 1 (RBX1)—COP9 signalsome complex subunit 8 (COPS8). We have proposed a model of inheritance for CENP-A ubiquitylation, through dimerization between rounds of cell divisions, that maintains the position of centromeres. Full article

(This article belongs to the Special Issue Protein-DNA Interactions: From Biophysics to Genomics)

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