Targeted and Genome-Scale Methylomics Reveals Gene Body Signatures in Human Cell Lines
Li, Jin Billy
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CitationBall, Madeleine Price, Jin Billy Li, Yuan Gao, Je-Hyuk Lee, Emily LeProust, In-Hyun Park, Bin Xie, George Quentin Daley, and George McDonald Church. 2009. Targeted and genome-scale methylomics reveals gene body signatures in human cell lines. Nature Biotechnology 27(4): 361-368.
AbstractCytosine methylation, an epigenetic modification of DNA, is a target of growing interest for developing high throughput profiling technologies. Here we introduce two new, complementary techniques for cytosine methylation profiling utilizing next generation sequencing technology: bisulfite padlock probes (BSPPs) and methyl sensitive cut counting (MSCC). In the first method, we designed a set of ~10,000 BSPPs distributed over the ENCODE pilot project regions to take advantage of existing expression and chromatin immunoprecipitation data. We observed a pattern of low promoter methylation coupled with high gene body methylation in highly expressed genes. Using the second method, MSCC, we gathered genome-scale data for 1.4 million HpaII sites and confirmed that gene body methylation in highly expressed genes is a consistent phenomenon over the entire genome. Our observations highlight the usefulness of techniques which are not inherently or intentionally biased in favor of only profiling particular subsets like CpG islands or promoter regions.
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