Research Article

Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

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Science  05 May 2017:
Vol. 356, Issue 6337, pp. 503-508
DOI: 10.1126/science.aag3260

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Inducing DNA methylation where it wasn't

The specific order of DNA's purines and pyrimidines encodes proteins, but chemically modified bases are important in regulating gene expression. In mammals, most cytosines are methylated when present in the CpG dinucleotide; however, stretches of mammalian DNA containing a high frequency of the CG sequence, termed CpG islands (CGIs), are typically unmethylated. The mechanism by which methylation of CGIs is blocked is unclear. Takahashi et al. interrupted CpG-rich sequences by targeted insertion of CpG-free DNA into CGIs in human pluripotent stem cells, which induced stable, heritable methylation. Some disorders result from improper methylation; this work provides an epigenome-editing tool to develop model systems for understanding CGI methylation in development and disease. It may also enable therapeutic strategies to correct aberrant imprinting diseases.

Science, this issue p. 503

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