Cell cycle-dependent 3D distribution of telomeres and telomere repeat-binding factor 2 (TRF2) in HaCaT and HaCaT-myc cells

Ermler, Sibylle; Krunic, Damir; Knoch, Tobias; Moshir, Sharareh; Mai, Sabine; Greulich-Bode, Karin M.; Boukamp, Petra

doi:10.1078/0171-9335-00430

Cited by 24 publications

(30 citation statements)

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“…Although yeast cells are known to form few large clusters at the heterochromatic nuclear border (9,10), most human telomeres have been shown to avoid the nuclear periphery (16,21). In line with this, we found that telomeres of living ECV-cells have a higher probability of localizing in the central part of the nuclear volume.…”

Section: Discussionsupporting

confidence: 80%

“…An increasing body of evidence shows that telomeres are organized in a nonrandom, cell-type, and cell cycle-dependent manner (16,20,21,44,45). Although yeast cells are known to form few large clusters at the heterochromatic nuclear border (9,10), most human telomeres have been shown to avoid the nuclear periphery (16,21).…”

Section: Discussionmentioning

confidence: 99%

“…Several aspects of telomere organization have been documented such as association (14)(15)(16), nuclear localization (17)(18)(19) and cell type and cell cycle dependence (16,(20)(21)(22). These data have mainly originated from fluorescence in situ hybridization (FISH) studies with pan-or subtelomeric probes or immunocytochemistry for telomere binding proteins, both methods inherently limited to fixed material and prone to preparation-related artifacts.…”

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confidence: 99%

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Controlled light exposure microscopy reveals dynamic telomere microterritories throughout the cell cycle

et al. 2008

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Telomeres are complex end structures that confer functional integrity and positional stability to human chromosomes. Despite their critical importance, there is no clear view on telomere organization in cycling human cells and their dynamic behavior throughout the cell cycle. We investigated spatiotemporal organization of telomeres in living human ECV-304 cells stably expressing telomere binding proteins TRF1 and TRF2 fused to mCitrine using four dimensional microscopy. We thereby made use of controlled light exposure microscopy (CLEM), a novel technology that strongly reduces photodamage by limiting excitation in parts of the image where full exposure is not needed. We found that telomeres share small territories where they dynamically associate. These territories are preferentially positioned at the interface of chromatin domains. TRF1 and TRF2 are abundantly present in these territories but not firmly bound. At the onset of mitosis, the bulk of TRF protein dissociates from telomere regions, territories disintegrate and individual telomeres become faintly visible. The combination of stable cell lines, CLEM and cytometry proved essential in providing novel insights in compartment-based nuclear organization and may serve as a model approach for investigating telomere-driven genome-instability and studying long-term nuclear dynamics. ' 2008 International Society for Advancement of Cytometry Key termstelomere; TRF1; TRF2; nuclear organization; chromatin dynamics; CLEM; live cell imaging TELOMERES are the natural ends of linear chromosomes. A mammalian telomere consists of a double stranded array of simple TTAGGG repeats ending in a single stranded overhang that folds back to form a T-loop structure (1). In combination with sufficient telomere repeats, a complex of indirect and direct telomere binding proteins, dubbed shelterin, assures proper telomere structure and function. The specificity of shelterin for telomeric DNA is due to the recognition of TTAGGG repeats by three of its components: the homodimers telomeric repeat binding factor 1 and 2 (TRF1 and TRF2) that bind the duplex part of telomeres, and protection of telomeres 1 that binds to the single stranded TTAGGG repeats present at the three-overhang and in the D loop of the T-loop configuration (2-5).The nucleus has a meticulous organization with functional relevance to the cell assuring proper gene expression, replication and genome stability (6-8). Telomeres are considered to play an important role in spatial genome organization. Whereas yeast telomeres are known to form few large silencing clusters at the heterochromatic nuclear periphery (9,10), there is no consensus on how telomeres are organized in the mammalian nucleus. From an architectural point of view, human telomeres have been proposed to be anchored to a nuclear scaffold, thereby possibly providing struc-

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Controlled light exposure microscopy reveals dynamic telomere microterritories throughout the cell cycle

et al. 2008

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“…Telomere dynamics has also been observed in interphase nuclei of human keratinocytes [Ermler et al, 2004]. Telomere movement is not only dependent on cell cycle but also on cell shape [Chuang et al, 2004;Ermler et al, 2004]. Thus, we conclude that telomeres are not static in mammalian nuclei but perform cell cycle and cell-type specific movements.…”

Section: Structural Organization Of Telomeres In Mammalian Nucleisupporting

confidence: 60%

“…Long ranging as well as short movements were observed over a time period of 20 min [Molenaar et al, 2003]. Telomere dynamics has also been observed in interphase nuclei of human keratinocytes [Ermler et al, 2004]. Telomere movement is not only dependent on cell cycle but also on cell shape [Chuang et al, 2004;Ermler et al, 2004].…”

Section: Structural Organization Of Telomeres In Mammalian Nucleimentioning

confidence: 99%

The significance of telomeric aggregates in the interphase nuclei of tumor cells

Mai

Garini

2006

J of Cellular Biochemistry

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Three‐dimensional nuclear telomere architecture changes during endometrial carcinoma development

Danescu

Gonzalez

Cristofano

et al. 2013

Genes Chromosomes & Cancer

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Endometrioid or type-I endometrial carcinoma (EC) develops from hyperproliferative glandular pathologies. Inactivation of the tumor suppressor gene PTEN is frequently associated with type-I EC. Using a previously characterized Pten heterozygous (Pten+/−) mouse model, this study investigates the three-dimensional (3D) telomere profiles during progression from hyperplastic lesions to EC to test the hypothesis that altered 3D telomere profiles can be detected prior to Pten loss in early hyperproliferative lesions. We used immunohistochemistry and 3D-telomere fluorescent in-situ hybridization to investigate Pten expression, telomere length and signal distribution, average number and spatial distribution of telomeres and formation of telomere aggregates in uterine glandular epithelial cells from wildtype and Pten+/− mice. Pten showed nuclear and cytoplasmic localization in WT, predominantly cytoplasmic staining in simple hyperplasia (SH) and was markedly reduced in atypical hyperplasia (AH). Telomere length in glandular epithelial cells does not shorten with age. The average number of telomeres per nucleus was not different in WT and Pten+/− mice indicating the lack of substantial numeric chromosome aberrations during EC development. We observed telomere aggregates in lesions of AH and EC. SH lesions in Pten+/− mice differed from normal glandular epithelium by an increased relative number of shorter telomeres and by a telomere signal distribution indicative of a heterogeneous cell population. Our study revealed that alterations in the nuclear 3D telomere architecture are present in early proliferative lesions of mouse uterine tissues indicative of EC development. The changes in telomere length distribution and nuclear signal distribution precede the loss of Pten. © 2013 Wiley Periodicals, Inc.

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Cell cycle-dependent 3D distribution of telomeres and telomere repeat-binding factor 2 (TRF2) in HaCaT and HaCaT-myc cells

Cited by 24 publications

References 32 publications

Controlled light exposure microscopy reveals dynamic telomere microterritories throughout the cell cycle

Controlled light exposure microscopy reveals dynamic telomere microterritories throughout the cell cycle

The significance of telomeric aggregates in the interphase nuclei of tumor cells

Three‐dimensional nuclear telomere architecture changes during endometrial carcinoma development

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