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Analytical Report
Estimating the Prevalence and Regulatory Potential of the Telomere Looping Effect in Yeast Transcription Regulation
M Madan Babu, S Balaji, Lakshminarayan M. Iyer and L Aravind
volume 5 | issue 20
15 october 2006Pages: 2354 - 2363
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Telomeres have long been implicated to have a functional role in the regulation of gene expression. Recent studies have reported that the looping back of telomeres or the telomere looping effect (TLE) can juxtapose genes and regulatory sequences separated by large distances on the same chromosome and facilitate long-distance control of gene expression. In this work we report a detailed investigation on the prevalence and regulatory potential of TLE on a genomic scale by assembling data on protein-DNA interactions from several large-scale ChIp-chip experiments in Saccharomyces cerevisiae. Analysis of the assembled data revealed that a statistically significant number of DNA segments that were inferred to interact with ten or more different transcription factors physically mapped to the ends (telomeric/sub-telomeric regions) from several chromosomes (19 of 32 chromosome ends). For the 83 transcription factors that were inferred to be cross-linked to these DNA segments, we found a statistically significant skew in the distribution of their inferred internal binding sites over the length of the chromosome, such that more than expected binding events occurred proximal to chromosomal ends than elsewhere. These observations suggest the telomere looping effect to be their most likely explanation and imply that a major fraction of the internally bound yeast transcription factors potentially interact with looped back telomeres. Further, we also identified several evolutionarily conserved components of the basal transcriptional machinery that are also frequently linked to these chromosome end segments, strengthening the proposal for a direct interaction between the chromosome ends and internally located transcriptional complexes. We also identified certain chromatin factors that might participate in the TLE and potentially modulate gene expression by chromatin modifications such as histone deacetylation. Our findings provide the first computational evidence for a significant role of long-range regulatory interactions due to telomere looping. These observations also suggest that genome-wide chromatin immunoprecipitation data could be used to systematically uncover regulatory effects of long-range chromatin.
Authors
M Madan Babu
National Institutes of Health, Bethesda, MD
S Balaji
National Institutes of Health, Bethesda, MD
Lakshminarayan M. Iyer
National Institutes of Health, Bethesda, MD
L Aravind
National Institutes of Health; Bethesda, MD
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.