Human telomeres are attached to the nuclear matrix.

Lange, Titia de

doi:10.1002/j.1460-2075.1992.tb05104.x

Cited by 315 publications

(196 citation statements)

References 72 publications

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“…DNA was digested with AluI and MboI, quantified using Hoechst fluorimetry, separated on a 0.7% agarose gel, and transferred to a Hybond-N membrane for hybridization using an [␣-32 P]dCTP Klenow-labeled 800-bp telomeric DNA probe from pSP73Sty11 (de Lange et al 1990;de Lange 1992). Blots were exposed to PhosphorImager screens, and mean telomeric restriction fragment lengths were determined using ImageQuan.…”

Section: Telomere Length Analysismentioning

confidence: 99%

POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex

Hockemeyer²,

Krutchinsky³

et al. 2004

Genes Dev.

395

412

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Human telomere length is controlled by a negative feedback loop based on the binding of TRF1 to doublestranded telomeric DNA. The TRF1 complex recruits POT1, a single-stranded telomeric DNA-binding protein necessary for cis-inhibition of telomerase. By mass spectrometry, we have identified a new telomeric protein, which we have named POT1-interacting protein 1 (PIP1). PIP1 bound both POT1 and the TRF1-interacting factor TIN2 and could tether POT1 to the TRF1 complex. Reduction of PIP1 or POT1 levels with shRNAs led to telomere elongation, indicating that PIP1 contributes to telomere length control through recruitment of POT1.Supplemental material is available at http://www.genesdev.org.

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Section: Telomere Length Analysismentioning

confidence: 99%

POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex

Hockemeyer²,

Krutchinsky³

et al. 2004

Genes Dev.

395

412

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“…tural stability to the nuclear interior (11)(12)(13). 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).…”

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confidence: 99%

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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“…Centromeric scaffold/matrix attachment has been shown to be sequence-independent, with the domain of increased S/MARs being mapped and shown to fully encompass the centromere-specific histone H3-related kinetochore protein domain of CENP-A on two human neocentromeres (21,22). Furthermore, scaffold/matrix attachment of telomere sequences has also been shown to be epigenetic (23).…”

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confidence: 99%

Effects of Scaffold/Matrix Alteration on Centromeric Function and Gene Expression

Sümer

Saffery

Wong

et al. 2004

Journal of Biological Chemistry

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We have previously described a 3.5-Mb domain of enhance scaffold/matrix attachment region (S/MAR) at a human neocentromere, and normal expression of underlying genes within this region. We also reported that partial inhibition of histone deacetylation using 33 nM trichostatin A (TSA) resulted in a shift in the position of the CENP-A-binding domain within the neocentromere, with no noticeable effects on mitotic segregation function. In this study, 33 nM TSA caused a reduction in the size of the enhanced S/MAR domain of one-half to 1.7 Mb. Treatment with a DNA-intercalating drug distamycin A (DST) at 75 g/ml resulted in a size reduction of the enhanced S/MAR domain at the neocentromere of twothirds to 1.2 Mb, and that of the CENP-A-binding domain of 40%, from 330 to 196 kb, with no significant shift in the position of the latter domain. Other DST effects include mitotic chromosomal missegregation, reduction in the levels of Topo II␣, CENP-A, CENP-C, and HP1␣, and an increase in mitotic checkpoint protein BubR1. TSA or DST treatment similarly resulted in a significant reduction, by ϳ20 and 50%, respectively, in the size of the enhanced S/MAR domain at the ␣-satellite DNA of a native chromosome 10 centromere. Transcriptional competence within the neocentromere is overall not noticeably altered by either TSA or DST treatment, as is evident from the absence of any significant increase or decrease in the expression levels of 47 underlying genes tested. These results suggest that a substantial contraction of the S/MAR domain may not be deleterious to centromere function, that disruption of the S/MAR domain directly affects the binding properties of a host of scaffold/matrix and centromeric/pericentric proteins, and that the overall competence and regulation of transcription at the neocentromeric chromatin is similar to those found at the corresponding normal genomic sites.

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Human telomeres are attached to the nuclear matrix.

Cited by 315 publications

References 72 publications

POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex

POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex

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

Effects of Scaffold/Matrix Alteration on Centromeric Function and Gene Expression

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