Estecio MR, Gallegos J, Vallot C et al.Genome architecture marked by retrotransposons modulates predisposition to DNA methylation in cancer. Genome Res 20:1369-1382

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Genome Research (Impact Factor: 14.63). 10/2010; 20(10):1369-82. DOI: 10.1101/gr.107318.110
Source: PubMed


Epigenetic silencing plays an important role in cancer development. An attractive hypothesis is that local DNA features may participate in differential predisposition to gene hypermethylation. We found that, compared with methylation-resistant genes, methylation-prone genes have a lower frequency of SINE and LINE retrotransposons near their transcription start site. In several large testing sets, this distribution was highly predictive of promoter methylation. Genome-wide analysis showed that 22% of human genes were predicted to be methylation-prone in cancer; these tended to be genes that are down-regulated in cancer and that function in developmental processes. Moreover, retrotransposon distribution marks a larger fraction of methylation-prone genes compared to Polycomb group protein (PcG) marking in embryonic stem cells; indeed, PcG marking and our predictive model based on retrotransposon frequency appear to be correlated but also complementary. In summary, our data indicate that retrotransposon elements, which are widespread in our genome, are strongly associated with gene promoter DNA methylation in cancer and may in fact play a role in influencing epigenetic regulation in normal and abnormal physiological states.

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    • "The strongest association of class I transposable elements with gene duplication is found within 5–10 kb distance from the respective genes [41]. In fact, there is evidence for duplication of such 5–10 kb regions for another class of chemosensory receptor genes [42]. "
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    • "Thus, retrotransposons may well be more ubiquitous than DNA in the mammalian genomes. It has been reported that retrotransposons are capable of retrotransposition in various primate genomes and thus they have a major impact on the architecture and fluidity of their host genomes (Cordaux et al. 2006; Estécio et al. 2010; Nekrutenko and Li 2001). "
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