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Old 05-15-2009, 05:00 AM   #1
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Related Articles An improved method for genome wide DNA methylation profiling correlated to transcription and genomic instability in two breast cancer cell lines.

BMC Genomics. 2009 May 13;10(1):223

Authors: Li J, Gao F, Li N, Li S, Yin G, Tian G, Jia S, Wang K, Zhang X, Yang H, Nielsen AL, Bolund L

ABSTRACT: BACKGROUND: DNA methylation is a widely studied epigenetic mechanism known to correlate with gene repression and genomic stability. Development of sensitive methods for global detection of DNA methylation events is of particular importance. RESULTS: We here describe a technique, called modified methylation-specific digital karyotyping (MMSDK) based on methylation-specific digital karyotyping (MSDK) with a novel sequencing approach. Briefly, after a tandem digestion of genomic DNA with a methylation-sensitive mapping enzyme and a fragmenting enzyme, short sequence tags are obtained. These tags are amplified, followed by direct, massively parallel sequencing (Solexa 1G Genome Analyzer). This method allows high-throughput and low-cost genome-wide DNA methylation mapping. We applied this method to investigate global DNA methylation profiles for widely used breast cancer cell lines, MCF-7 and MDA-MB-231, which are representatives for luminal-like and mesenchymal-like cancer types, respectively. By comparison, a highly similar overall DNA methylation pattern was revealed for the two cell lines. However a cohort of individual genomic loci with significantly different DNA methylation profile between two cell lines was identified. Furthermore, we revealed a genome-wide significant correlation between gene expression and the methylation status of gene promoters with CpG islands (CGIs) in the two cancer cell lines, and a correlation of gene expression and the methylation status of promoters without CGIs in MCF-7 cells. CONCLUSIONS: The MMSDK method will be a valuable tool to increase the current knowledge of genome wide DNA methylation profiles.

PMID: 19439076 [PubMed - as supplied by publisher]



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