Subtelomeric Elements Influence But Do Not Determine Silencing Levels at Saccharomyces cerevisiae Telomeres

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Genetics (Impact Factor: 5.96). 01/2008; 177(4):2541-6. DOI: 10.1534/genetics.107.079806
Source: PubMed


In Saccharomyces cerevisiae, genes placed near telomeres are transcriptionally repressed (telomere position effect, TPE). Although telomeric DNA sequence is the same at all chromosome ends, the subtelomeric elements (STEs) and level of TPE vary from telomere to telomere. We tested whether STEs determine TPE levels. STEs contributed to TPE, as deleting the X element from the VI-R telomere modestly decreased silencing at this telomere. However, STEs were not the major determinant of TPE levels, as inserting the VI-R X element at the truncated VII-L telomere did not increase TPE. These data suggest that the TPE levels of individual telomeres are dependent on some aspect of chromosome context.

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Available from: Michelle A Mondoux, Aug 14, 2014
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    • "These results seem to rule out a critical role for tethering in TPE (Ferreira et al. 2011). This conclusion is consistent with experiments indicating that TPE and tethering are separable phenotypes (Tham et al. 2001; Mondoux and Zakian 2007). However, this conclusion is still surprising , given numerous examples in diverse organisms for a connection between the nuclear periphery, heterochromatin formation, and gene silencing. "
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    • "The recent study by Takahashi et al. (63) pointed out that a modified telomere could differ from a natural one. We then examined the association of 13Myc-tagged Sir2 with natural telomeres VIIL, VIR and IIIR in wild-type and Mediator mutant strains (64,65) (Figure 4A–C). The natural telomere VIIL (n7L) contains a ∼0.75 kb X element adjacent to the TG1-3 repeats at the chromosome end (Figure 4A). "
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    • "However, a catalytically inactive methyltransferase domain (Dot1172-582 G401R) did not disrupt silencing (Figure 2D-E). Different native telomeres and truncated telomeres can show different silencing properties, Sir protein binding, and nucleosome positioning [29,53,54]. To test whether the derepressor activity of Dot1 is a general property or is restricted to the truncated telomere used here, LexA operators and the URA3 gene were introduced at three different native chromosome ends. "
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    ABSTRACT: Methylation of histone H3 lysine 79 (H3K79) by Dot1 is highly conserved among species and has been associated with both gene repression and activation. To eliminate indirect effects and examine the direct consequences of Dot1 binding and H3K79 methylation, we investigated the effects of targeting Dot1 to different positions in the yeast genome. Targeting Dot1 did not activate transcription at a euchromatic locus. However, chromatin-bound Dot1 derepressed heterochromatin-mediated gene silencing over a considerable distance. Unexpectedly, Dot1-mediated derepression was established by both a H3K79 methylation-dependent and a methylation-independent mechanism; the latter required the histone acetyltransferase Gcn5. By monitoring the localization of a fluorescently tagged telomere in living cells, we found that the targeting of Dot1, but not its methylation activity, led to the release of a telomere from the repressive environment at the nuclear periphery. This probably contributes to the activity-independent derepression effect of Dot1. Targeting of Dot1 promoted gene expression by antagonizing gene repression through both histone methylation and chromatin relocalization. Our findings show that binding of Dot1 to chromatin can positively affect local gene expression by chromatin rearrangements over a considerable distance.
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