A human interstitial telomere associates in vivo with specific TRF2 and TIN2 proteins

Mignon-Ravix, Cécile; Depétris, D.; Delobel, Bruno; Croquette, Marie‐Françoise; Mattei, Marie-Genevı̀eve

doi:10.1038/sj.ejhg.5200775

Cited by 27 publications

(20 citation statements)

References 34 publications

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“…These nontelomeric functions might be, at least partially, explained by their binding to ITSs. Indeed, there is mounting indication that shelterin components can bind to interstitial DNA sequences: (i) TRF1 and TRF2 bind to the pericentromeric regions of hamster chromosomes containing large blocks of ITSs [23,24]; (ii) TRF2 and TIN2 bind to an ITS formed by a rare human chromosome rearrangement [25]; (iii) TRF2 binds to a stretch of telomeric sequence that is artificially inserted in the middle of the long arm of chromosome 4 [26]; (iv) Rap1 binds to several ITSs of the mouse genome [27]. However, three naturally occurring ITSs of human chromosomes do not appear to be bound by TRF2 [26].…”

Section: Thomas Simonet Et Al 1029mentioning

confidence: 99%

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Simonet¹,

Zaragosi²,

Philippe³

et al. 2011

Cell Res

135

146

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The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms involved in chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extratelomeric sites contains interstitial telomeric sequences (or ITSs). However, we also identified non-ITS sites, which correspond to centromeric and pericentromeric satellite DNA. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks by binding to extratelomeric sequences.

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Section: Thomas Simonet Et Al 1029mentioning

confidence: 99%

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Simonet¹,

Zaragosi²,

Philippe³

et al. 2011

Cell Res

135

146

View full text Add to dashboard Cite

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“…20 Fibroblasts were trypsinized, rinsed and resuspended in PBS (pH 7.2), but were then treated as the other cell types. Cells were centrifugated (300 t/min for 5 min) onto polylysine-coated slides in cytospin 3 (Shandon, Cergy-Pontoise, France), then fixed at room temperature (RT) for 10 min in 2% (w/v) paraformaldehyde/PBS (pH 7.2).…”

Section: Immunocytochemistrymentioning

confidence: 99%

“…20 After immunocytochemistry, all preparations were fixed with 1% (w/v) paraformaldehyde in PBS for 5 min, rinsed again before staining with DAPI (100 ng/ml) diluted in Vectashield (Vector Laboratories). All antibodies were tested in individual staining reactions for their specificity and performance.…”

Section: Immunocytochemistrymentioning

confidence: 99%

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Subcellular distribution of HP1 proteins is altered in ICF syndrome

et al. 2004

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The Immunodeficiency, Centromeric instability, and Facial (ICF) syndrome is a rare autosomal recessive disorder that results from mutations in the DNMT3B gene, encoding a DNA-methyltransferase that acts on GC-rich satellite DNAs. This syndrome is characterized by immunodeficiency, facial dysmorphy, mental retardation of variable severity and chromosomal abnormalities that essentially involve juxtacentromeric heterochromatin of chromosomes 1 and 16. These abnormalities demonstrate that hypomethylation of satellite DNA can induce alterations in the structure of heterochromatin. In order to investigate the effect of DNA hypomethylation on heterochromatin organization, we analyzed the in vivo distribution of HP1 proteins, essential components of heterochromatin, in three ICF patients. We observed that, in a large proportion of ICF G2 nuclei, all HP1 isoforms show an aberrant signal concentrated into a prominent bright focus that co-localizes with the undercondensed 1qh or 16qh heterochromatin. We found that SP100, SUMO-1 and other proteins from the promyelocytic leukemia nuclear bodies (NBs) form a large body that co-localizes with the HP1 signal. This is the first description of altered nuclear distribution of HP1 proteins in the constitutional ICF syndrome. Our results show that satellite DNA hypomethylation does not prevent HP1 proteins from associating with heterochromatin. They suggest that, at G2 phase, HP1 proteins are involved in the heterochromatin condensation and may therefore remain concentrated at these sites until the condensation is complete. They also indicate that proteins from the NB could play a role in this process. Finally, satellite DNA length polymorphism could affect the efficiency of heterochromatin condensation and thus contribute to the variability of the ICF phenotype.

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“…Thus, the ITSs could also correspond to sites of spontaneous and induced chromosome breakage, conferring fragility to the region where they are inserted. At the molecular level, it has been shown that some proteins of the shelterin complex, such as TRF1, TRF2, and RAP1, can also locate to ITSs (Zakian 1995;Mignon-Ravix et al 2002;Krutilina et al 2003;Simonet et al 2011;Bosco and de Lange 2012), suggesting a role of these proteins in the organization and/or functioning of heterochromatic ITSs. In this sense, for example, the shelterin protein TRF1 is fundamental to preventing TTAGGG-repeat replication problems and protecting telomeres from breaking (Sfeir et al 2009).…”

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confidence: 99%

Chromatin Organization and Remodeling of Interstitial Telomeric Sites During Meiosis in the Mongolian Gerbil (Meriones unguiculatus)

et al. 2014

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Telomeric DNA repeats are key features of chromosomes that allow the maintenance of integrity and stability in the telomeres. However, interstitial telomere sites (ITSs) can also be found along the chromosomes, especially near the centromere, where they may appear following chromosomal rearrangements like Robertsonian translocations. There is no defined role for ITSs, but they are linked to DNA damage-prone sites. We were interested in studying the structural organization of ITSs during meiosis, a kind of cell division in which programmed DNA damage events and noticeable chromatin reorganizations occur. Here we describe the presence of highly amplified ITSs in the pericentromeric region of Mongolian gerbil (Meriones unguiculatus) chromosomes. During meiosis, ITSs show a different chromatin conformation than DNA repeats at telomeres, appearing more extended and accumulating heterochromatin markers. Interestingly, ITSs also recruit the telomeric proteins RAP1 and TRF1, but in a stage-dependent manner, appearing mainly at late prophase I stages. We did not find a specific accumulation of DNA repair factors to the ITSs, such as gH2AX or RAD51 at these stages, but we could detect the presence of MLH1, a marker for reciprocal recombination. However, contrary to previous reports, we did not find a specific accumulation of crossovers at ITSs. Intriguingly, some centromeric regions of metacentric chromosomes may bind the nuclear envelope through the association to SUN1 protein, a feature usually performed by telomeres. Therefore, ITSs present a particular and dynamic chromatin configuration in meiosis, which could be involved in maintaining their genetic stability, but they additionally retain some features of distal telomeres, provided by their capability to associate to telomere-binding proteins.

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A human interstitial telomere associates in vivo with specific TRF2 and TIN2 proteins

Cited by 27 publications

References 34 publications

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Subcellular distribution of HP1 proteins is altered in ICF syndrome

Chromatin Organization and Remodeling of Interstitial Telomeric Sites During Meiosis in the Mongolian Gerbil (Meriones unguiculatus)

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