scholarly journals Regulation of the Human Telomerase Gene TERT by Telomere Position Effect—Over Long Distances (TPE-OLD): Implications for Aging and Cancer

PLoS Biology ◽  
2016 ◽  
Vol 14 (12) ◽  
pp. e2000016 ◽  
Author(s):  
Wanil Kim ◽  
Andrew T. Ludlow ◽  
Jaewon Min ◽  
Jerome D. Robin ◽  
Guido Stadler ◽  
...  
Keyword(s):  
Position Effect ◽  
Telomere Position Effect ◽  
Human Telomerase

scholarly journals ATR-16 syndrome: mechanisms linking monosomy to phenotype

2020 ◽  
Vol 57 (6) ◽  
pp. 414-421 ◽  
Author(s):  
Christian Babbs ◽  
Jill Brown ◽  
Sharon W Horsley ◽  
Joanne Slater ◽  
Evie Maifoshie ◽  
...  
Keyword(s):  
Genetic Background ◽  
Position Effect ◽  
Distal Region ◽  
Chromosome 16 ◽  
Developmental Abnormalities ◽  
Telomere Position Effect ◽  
Contiguous Gene ◽  
Wide Range ◽  
Genetic Background Effects ◽  
Critical Regions

BackgroundDeletions removing 100s–1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases, understanding the contribution of the deletion to an individual’s clinical phenotype is challenging.MethodsHere, as an example of this common phenomenon, we analysed 41 patients with simple deletions of ~177 to ~2000 kb affecting one allele of the well-characterised, gene dense, distal region of chromosome 16 (16p13.3), referred to as ATR-16 syndrome. We characterised deletion extents and screened for genetic background effects, telomere position effect and compensatory upregulation of hemizygous genes.ResultsWe find the risk of developmental and neurological abnormalities arises from much smaller distal chromosome 16 deletions (~400 kb) than previously reported. Beyond this, the severity of ATR-16 syndrome increases with deletion size, but there is no evidence that critical regions determine the developmental abnormalities associated with this disorder. Surprisingly, we find no evidence of telomere position effect or compensatory upregulation of hemizygous genes; however, genetic background effects substantially modify phenotypic abnormalities.ConclusionsUsing ATR-16 as a general model of disorders caused by CNVs, we show the degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but depends on their genetic background. We also show there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome and this has important implications for genetic counselling.

scholarly journals Transcriptional Activity of the Telomeric Retrotransposon HeT-A in Drosophila melanogaster Is Stimulated as a Consequence of Subterminal Deficiencies at Homologous and Nonhomologous Telomeres

2007 ◽  
Vol 27 (13) ◽  
pp. 4991-5001 ◽  
Author(s):  
Radmila Capkova Frydrychova ◽  
Harald Biessmann ◽  
Alexander Y. Konev ◽  
Mikhail D. Golubovsky ◽  
Jessica Johnson ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Promoter Activity ◽  
Transcriptional Activity ◽  
Position Effect ◽  
Wild Type ◽  
Global Effect ◽  
Transcript Levels ◽  
Telomere Position Effect

ABSTRACT Drosophila melanogaster telomeres have two DNA domains: a terminal array of retrotransposons and a subterminal repetitive telomere-associated sequence (TAS), a source of telomere position effect (TPE). We reported previously that deletion of the 2L TAS array leads to dominant suppression of TPE by stimulating in trans expression of a telomeric transgene. Here, we compared the transcript activities of a w transgene inserted between the retrotransposon and TAS arrays at the 2L telomere in genotypes with different lengths of the 2L TAS. In contrast to individuals bearing a wild-type 2L homologue, flies with a TAS deficiency showed a significant increase in the level of telomeric w transcript during development, especially in pupae. Moreover, we identified a read-through w transcript initiated from a retrotransposon promoter in the terminal array. Read-through transcript levels also significantly increased with the presence of a 2L TAS deficiency in trans, indicating a stimulating force of the TAS deficiency on retrotransposon promoter activity. The read-through transcript contributes to total w transcript, although most w transcript originates at the w promoter. While silencing of transgenes in nonhomologous telomeres is suppressed by 2L TAS deficiencies, suggesting a global effect, the overall level of HeT-A transcripts is not increased under similar conditions.

scholarly journals TEL2, an essential gene required for telomere length regulation and telomere position effect in Saccharomyces cerevisiae.

1996 ◽  
Vol 16 (6) ◽  
pp. 3094-3105 ◽  
Author(s):  
K W Runge ◽  
V A Zakian
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Sequences ◽  
Transcriptional Repression ◽  
Protein Complexes ◽  
Essential Gene ◽  
Position Effect ◽  
Repeated Sequence ◽  
Telomeric Dna ◽  
Telomere Position Effect ◽  
Telomere Lengthening

The DNA-protein complexes at the ends of linear eukaryotic chromosomes are called the telomeres. In Saccharomyces cerevisiae, telomeric DNA consists of a variable length of the short repeated sequence C1-3A. The length of yeast telomeres can be altered by mutation, by changing the levels of telomere binding proteins, or by increasing the amount of C1-3A DNA sequences. Cells bearing the tel1-1 or tel2-1 mutations, known previously to have short telomeres, did not respond to perturbations that caused telomere lengthening in wild-type cells. The transcription of genes placed near yeast telomeres is reversibly repressed, a phenomenon called the telomere position effect. The tel2-1 mutation reduced the position effect but did not affect transcriptional repression at the silent mating type cassettes, HMRa and HML alpha. The TEL2 gene was cloned, sequenced, and disrupted. Cells lacking TEL2 function died, with some cells arresting as large cells with three or four small protrusions or "blebs."

scholarly journals ATR16 Syndrome: Mechanisms Linking Monosomy to Phenotype

2019 ◽  
Author(s):  
Christian Babbs ◽  
Jill Brown ◽  
Sharon W. Horsley ◽  
Joanne Slater ◽  
Evie Maifoshie ◽  
...  
Keyword(s):  
Genetic Background ◽  
Position Effect ◽  
Distal Region ◽  
Copy Number Variations ◽  
Chromosome 16 ◽  
Developmental Abnormalities ◽  
Telomere Position Effect ◽  
Wide Range ◽  
Genetic Background Effects ◽  
Critical Regions

AbstractBackgroundSporadic deletions removing 100s-1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases, understanding the contribution of the deletion to an individual’s clinical phenotype is challenging.MethodsHere, as an example of this common phenomenon, we analysed 34 patients with simple deletions of ∼177 to ∼2000 kb affecting one allele of the well characterised, gene dense, distal region of chromosome 16 (16p13.3), referred to as ATR-16 syndrome. We characterised precise deletion extent and screened for genetic background effects, telomere position effect and compensatory up regulation of hemizygous genes.ResultsWe find the risk of developmental and neurological abnormalities arises from much smaller terminal chromosome 16 deletions (∼400 kb) than previously reported. Beyond this, the severity of ATR-16 syndrome increases with deletion size, but there is no evidence that critical regions determine the developmental abnormalities associated with this disorder. Surprisingly, we find no evidence of telomere position effect or compensatory upregulation of hemizygous genes, however, genetic background effects substantially modify phenotypic abnormalities.ConclusionsUsing ATR-16 as a general model of disorders caused by sporadic copy number variations, we show the degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but also depends on their genetic background. We also show there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome and this has important implications for genetic counselling.

Analysis of Mammalian Telomere Position Effect

2004 ◽  
pp. 121-136 ◽  
Author(s):  
Joseph A. Baur ◽  
Woodring E. Wright ◽  
Jerry W. Shay
Keyword(s):  
Position Effect ◽  
Telomere Position Effect

scholarly journals Extra telomeres, but not internal tracts of telomeric DNA, reduce transcriptional repression at Saccharomyces telomeres.

Genetics ◽  
1995 ◽  
Vol 139 (1) ◽  
pp. 67-79 ◽  
Author(s):  
E A Wiley ◽  
V A Zakian
Keyword(s):  
Chromatin Structure ◽  
Transcriptional Repression ◽  
Specific Binding ◽  
Position Effect ◽  
Telomeric Dna ◽  
Deletion Derivative ◽  
Telomere Position Effect ◽  
Binding Factor ◽  
In Trans ◽  
Different Strains

Abstract Yeast telomeric DNA is assembled into a nonnucleosomal chromatin structure known as the telosome, which is thought to influence the transcriptional repression of genes placed in its vicinity, a phenomenon called telomere position effect (TPE). The product of the RAP1 gene, Rap1p, is a component of the telosome. We show that the fraction of cells exhibiting TPE can be substantially reduced by expressing large amounts of a deletion derivative of Rap1p that is unable to bind DNA, called Rap1 delta BBp, or by introducing extra telomeres on a linear plasmid, presumably because both compete in trans with telomeric chromatin for factor(s) important for TPE. This reduction in TPE, observed in three different strains, was demonstrated for two different genes, each assayed at a different telomere. In contrast, the addition of internal tracts of telomeric DNA on a circular plasmid had very little effect on TPE. The product of the SIR3 gene, Sir3p, appears to be limiting for TPE. Overexpression of Sir3p completely suppressed the reduction in TPE observed with expression of Rap1 delta BBp, but did not restore high levels of TPE to cells with extra telomeres. These results suggest that extra telomeres must titrate a factor other than Sir3p that is important for TPE. These results also provide evidence for a terminus-specific binding factor that is a factor with a higher affinity for DNA termini than for nonterminal tracts of telomeric DNA and indicate that this factor is important for TPE.

The yeast GAL11 protein is involved in regulation of the structure and the position effect of telomeres

1994 ◽  
Vol 14 (6) ◽  
pp. 3791-3799
Author(s):  
Y Suzuki ◽  
M Nishizawa
Keyword(s):  
Transcription Factor ◽  
Chromatin Structure ◽  
Position Effect ◽  
Regulation Of Transcription ◽  
Telomeric Region ◽  
Multicopy Plasmid ◽  
Telomere Position Effect ◽  
Dam Methylase ◽  
Delta Cells ◽  
Target Promoters

GAL11 is an auxiliary transcription factor that functions either positively or negatively, depending on the structure of the target promoters and the combination of DNA-bound activators. In this report, we demonstrate that a gal11 delta mutation caused a decrease in the length of the telomere C1-3A tract, a derepression of URA3 when it is placed next to telomere, and an increase in accessibility of the telomeric region to dam methylase, indicating that GAL11 is involved in the regulation of the structure and the position effect of telomeres. The defective position effect in a gal11 delta strain was suppressed by overproduction of SIR3, whereas overexpression of GAL11 failed to restore the telomere position effect in a sir3 delta strain. Hyperproduced GAL11 could partially suppress the defect in silencing at HMR in a sir1 delta mutant but not that in a sir3 delta mutant, suggesting that GAL11 can replace SIR1 function partly in the silencing of HMR. Overproduced SIR3 also could restore silencing at HMR in sir1 delta cells. In contrast, SIR1 in a multicopy plasmid relieved the telomere position effect, especially in a gal11 delta mutant. Since chromatin structure is thought to play a major role in the silencing at both the HM loci and telomeres, GAL11 is likely to participate in the regional regulation of transcription by the HM loci and telomeres, GAL11 is likely to participate in the regional regulation of transcription by modulating the chromatin structure.

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