Laser confocal microscopy analysis of human interphase nuclei by three-dimensional FISH reveals dynamic perinucleolar clustering of telomeres

Ramírez, María-José; Surrallés, Jordi

doi:10.1159/000167809

Cited by 23 publications

(17 citation statements)

References 48 publications

(15 reference statements)

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“…Centromeres have a unique chromatin composition (Bergmann et al 2012), which may modulate NL interactions. Human telomeres are not typically found at the periphery (Luderus et al 1996;Weierich et al 2003;Ramirez and Surralles 2008), consistent with their relatively low (50%) A/T content. Mouse telomeres, which have the same sequence, can be peripheral to some degree (Vourc'h et al 1993;Weierich et al 2003), but much of this is accounted for by the telocentric nature of mouse chromosomes (i.e., half of the telomeres are linked to pericentric regions, which tend to be peripheral).…”

Section: Discussionmentioning

confidence: 78%

Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence

et al. 2012

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In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this “A/T rule” in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.

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Section: Discussionmentioning

confidence: 78%

Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence

et al. 2012

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“…Clustering of short telomeres has been involved in the formation of micronuclei, nucleoplasmic bridges, and nuclear buds [91]. Some evidence suggests that telomere positioning is one of the determinant factors governing chromosome territory [29,91,92,93] whose disruption can affect gene expression [94], generate chromosomal abnormalities [29] and disrupt cell function [95]. Moreover, telomeres occupy microterritories throughout the cell cycle, forming groups of telomeres that have peripheral location.…”

Section: Telomeric Nuclear Organizationmentioning

confidence: 99%

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Samassékou

2013

Cancers

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the t(9;22) translocation. As in most cancers, short telomeres are one of the features of CML cells, and telomere shortening accentuates as the disease progresses from the chronic phase to the blastic phase. Although most individual telomeres are short, some of them are lengthened, and long individual telomeres occur non-randomly and might be associated with clonal selection. Telomerase is the main mechanism used to maintain telomere lengths, and its activity increases when CML evolves toward advanced stages. ALT might be another mechanism employed by CML cells to sustain the homeostasis of their telomere lengths and this mechanism seems predominant at the early stage of leukemogenesis. Also, telomerase and ALT might jointly act to maintain telomere lengths at the chronic phase, and as CML progresses, telomerase becomes the major mechanism. Finally, CML cells display an altered nuclear organization of their telomeres which is characterized by the presence of high number of telomeric aggregates, a feature of genomic instability, and differential positioning of telomeres. CML represents a good model to study mechanisms responsible for dynamic changes of individual telomere lengths and the remodeling of telomeric nuclear organization throughout cancer progression.

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“…Telomere ends of some chromosomes in Chinese hamster embryonic cells were preferentially organized in clusters [51]. Telomeres of NOR-containing acrocentric chromosomes in human lymphocytes usually cluster at the periphery of nucleoli [52]. Telomeric associations were observed in normal human fibroblasts, and the number of associations in non-cycling cells was increased in comparison with replicating cells [53].…”

Section: Discussionmentioning

confidence: 99%

Characterization of telomeric repeats in metaphase chromosomes and interphase nuclei of Syrian Hamster Fibroblasts

et al. 2012

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BackgroundRodents have been reported to contain large arrays of interstitial telomeric sequences (TTAGGG)n (ITS) located in pericentromeric heterochromatin. The relative sizes of telomeric sequences at the ends of chromosomes (TS) and ITS in Syrian hamster (Mesocricetus auratus) cells have not been evaluated yet, as well as their structural organization in interphase nuclei.ResultsFISH signal distribution analysis was performed on DAPI-banded metaphase chromosomes of Syrian hamster fibroblasts, and relative lengths of telomere signals were estimated. Besides well-distinguished FISH signals from ITS located on chromosomes ##2, 4, 14, 20 and X that we reported earlier, low-intensity FISH signals were visualized with different frequency of detection on all other metacentric chromosomes excluding chromosome #21. The analysis of 3D-distribution of TS in interphase nuclei demonstrated that some TS foci formed clearly distinguished associations (2–3 foci in a cluster) in the nuclei of cells subjected to FISH or transfected with the plasmid expressing telomeric protein TRF1 fused with GFP. In G0 and G1/early S-phase, the average total number of GFP-TRF1 foci per nucleus was less than that of PNA FISH foci in the corresponding cell cycle phases suggesting that TRF1 overexpression might contribute to the fusion of neighboring telomeres. The mean total number of GFP-TRF1 and FISH foci per nucleus was increased during the transition from G0 to G1/early S-phase that might be the consequence of duplication of some TS.ConclusionsThe relative lengths of TS in Syrian hamster cells were found to be moderately variable. All but one metacentric chromosomes contain ITS in pericentromeric heterochromatin indicating that significant rearrangements of ancestral genome occurred in evolution. Visualization of GFP-TRF1 fibrils that formed bridges between distinct telomeric foci allowed suggesting that telomere associations observed in interphase cells are reversible. The data obtained in the study provide the further insight in the structure and dynamics of telomeric sequences in somatic mammalian cells.

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Laser confocal microscopy analysis of human interphase nuclei by three-dimensional FISH reveals dynamic perinucleolar clustering of telomeres

Cited by 23 publications

References 48 publications

Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence

Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence

Dynamic Length Changes of Telomeres and Their Nuclear Organization in Chronic Myeloid Leukemia

Characterization of telomeric repeats in metaphase chromosomes and interphase nuclei of Syrian Hamster Fibroblasts

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