Principles of 3D chromosome folding and evolutionary genome reshuffling in mammals

Álvarez-González, Lucía; Arias-Sardá, Cristina; Montes-Espuña, Laia; Marín-Gual, Laia; Vara, Covadonga; Lister, Nicholas C.; Cuartero, Yasmina; García, Francisca; Deakin, Janine E.; Renfree, Marilyn B.; Robinson, Terence J.; Martí‐Renom, Marc A.; Waters, Paul D.; Farré, Marta; Ruiz‐Herrera, Aurora

doi:10.1016/j.celrep.2022.111839

Cited by 20 publications

(12 citation statements)

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“…If the cellular levels of the proteins that are responsible for loop formation Considering that SMC proteins are responsible for the formation of a dynamic loop topology, 25,28 the expression levels of these proteins and their residence times can be correlated with the amount of loop per chromosome. 26,35 In this case, it is conceivable to think of a scenario, in which the over-expression of these proteins (e.g., shorter loops) can change the shape of the cell nucleus. A future study with deformable shell models can enlighten the morphological effects of loop-forming proteins.…”

Section: Discussionmentioning

confidence: 99%

“…More recent studies have revealed that cellular concentration of loop-forming SMC proteins affects chromosome organization and even generates a distinction between various species. 26,34,35 This suggests that the degree of polymerization or/and the effective grafting density of cyclic polymers, both of which can be controlled by structural nuclear proteins, can provide a polymer-physics perspective on how the genome is arranged within a nearly spherical nucleus that is roughly the size of several tens of microns.…”

Section: Introductionmentioning

confidence: 99%

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Cyclic-polymer grafted colloids in spherical confinement: insights for interphase chromosome organization

Paturej

Erbaş

2023

Preprint

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Interphase chromosome structures are known to remain segregated in the micron-sized eukaryotic cell nucleus and occupy a certain fraction of nuclear volume, often without mixing. Using extensive coarse-grained simulations, we model such chromosome structures as colloidal particles whose surfaces are grafted by cyclic polymers. This model system is known as Rosetta. The cyclic polymers, with varying polymerization degrees, mimic the functionality of structural protein complexes, while the rigid core models the chromocenter sections of chromosomes. Our simulations show that the colloidal chromosome model provides a well-segregated particle distribution without specific attraction between the chain monomers. Notably, linear-polymer grafted particles also provide the same segregation scheme. However, unlike linear chains, cyclic chains result in less contact between the polymer layers of neighboring chromosome particles, demonstrating the effect of DNA breaks in altering genome-wide contacts. As the polymerization degree of the chains decreases while maintaining the total chromosomal length (the total polymer length per particle), particles form quasi-crystalline order, reminiscent of a glassy state. This order weakens for polymer chains with a characteristic size on the order of the confinement radius. Our simulations demonstrate that polymer systems can help decipher 3D chromosomal architectures along with fractal globular and loop-extrusion models.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclic-polymer grafted colloids in spherical confinement: insights for interphase chromosome organization

Paturej

Erbaş

2023

Preprint

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“…M. eugenii could be using more PRDM9-dependent hotspots, which would be expected to result in a more uniform distribution of DSBs along chromosomes. This even distribution in M. eugenii be also related to the extensive genomic reorganizations experienced in the family Macropodidae (Deakin, 2018;Deakin and O'Neill, 2020;Álvarez-González et al, 2022). In fact, recent reports have shown that lineage-specific evolutionary genomic reshuffling can influence patterns of higher-order chromatin organization (Farré et al, 2015;Álvarez-González et al, 2022), and that chromosomal reorganizations can have an impact on the three-dimensional genome folding and recombination in the germ line (Vara et al, 2021;Álvarez-González et al, 2022).…”

Section: Figure 10mentioning

confidence: 92%

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

Valero-Regalón

Solé

López-Jiménez

et al. 2023

Front. Cell Dev. Biol.

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In eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (Thylamys elegans, Dromiciops gliorides, and Macropus eugenii) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American species T. elegans and D. gliroides, chromosomal ends were conspicuously polarized in a bouquet configuration and synapsis progressed exclusively from the telomeres towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophase I in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representative M. eugenii, the bouquet polarization was incomplete and ephemeral, γH2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position of T. elegans, it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split of D. gliroides and the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.

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“…eugenii could be using more PRDM9-dependent hotspots, which would be expected to result in a more uniform distribution of DSBs along chromosomes. This even distribution in M. eugenii could be also related to the extensive genomic reorganizations experienced in the family Macropodidae (Deakin, 2018;Deakin and O'Neill, 2020;Álvarez-González et al, 2022). In fact, recent reports have shown that lineage-specific evolutionary genomic reshuffling can influence patterns of higher-order chromatin organization (Farré et al, 2015;Álvarez-González et al, 2022), and that chromosomal reorganizations can have an impact on the three-dimensional genome folding and recombination in the germ line (Vara et al, 2021;Álvarez-González et al, 2022).…”

Section: Differential Chromosomal Distribution Of Meiotic Dsbs In Mar...mentioning

confidence: 94%

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

Valero-Regalón

Solé

López-Jiménez

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

In eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (Thylamys elegans, Dromiciops gliorides, and Macropus eugenii) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American species T. elegans and D. gliroides, synapsis progressed exclusively from the chromosomal ends towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends, which appeared conspicuously polarized in a bouquet configuration at early stages of prophase I. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophaseI in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representative M. eugenii, γH2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position of T. elegans, it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split of D. gliroides and the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.

show abstract

Principles of 3D chromosome folding and evolutionary genome reshuffling in mammals

Cited by 20 publications

References 82 publications

Cyclic-polymer grafted colloids in spherical confinement: insights for interphase chromosome organization

Cyclic-polymer grafted colloids in spherical confinement: insights for interphase chromosome organization

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

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