Article

Unstable tandem repeats in promoters confer transcriptional evolvability

FAS Center for Systems Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
Science (Impact Factor: 31.48). 06/2009; 324(5931):1213-6. DOI: 10.1126/science.1170097
Source: PubMed

ABSTRACT Relative to most regions of the genome, tandemly repeated DNA sequences display a greater propensity to mutate. A search for tandem repeats in the Saccharomyces cerevisiae genome revealed that the nucleosome-free region directly upstream of genes (the promoter region) is enriched in repeats. As many as 25% of all gene promoters contain tandem repeat sequences. Genes driven by these repeat-containing promoters show significantly higher rates of transcriptional divergence. Variations in repeat length result in changes in expression and local nucleosome positioning. Tandem repeats are variable elements in promoters that may facilitate evolutionary tuning of gene expression by affecting local chromatin structure.

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    • "Simple repeats (2094), which included microsatellites and minisatellites, were the next most frequent type of repeat in the current RN genome assembly. Microsatellites have been shown to play roles in the evolution of organisms (Verstrepen et al. 2005; Vinces et al. 2009). They are also subject to changes in length. "
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    • "Furthermore, tandem repeat elements located in coding regions have been shown to influence expression of genes, including cancer-related genes, such as PCA3 and PTTG1IP (Fondon and Garner, 2004; Verstrepen et al., 2005; ZHou et al., 2011; Xiang et al., 2012). Vinces et al. suggested that promoter-associated tandem repeats may facilitate evolutionary tuning of gene expression by mediating elevated responsiveness to changing environmental conditions (Vinces et al., 2009). Yauk et al. indicated that expanded simple tandem repeats (ETSR) could serve as a sensitive biomarker of environmental exposure, and observed mutation and hypermethylation of ETSR in spermatogonial stem cells from mice exposed to particulate air pollution (Yauk et al., 2002, 2004, 2008). "
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