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BMC Genomics

, 10:223

First Online: 13 May 2009Received: 24 July 2008Accepted: 13 May 2009


BackgroundDNA 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.

ResultsWe 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 status 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.

ConclusionThe MMSDK method will be a valuable tool to increase the current knowledge of genome wide DNA methylation profiles.

AbbreviationsMSDKmethylation-specific digital karyotyping

MMSDKmodified methylation-specific digital karyotyping

CNVcopy number variation

SAGEserial analysis of gene expression


aCGHarray comparative genomic hybridization


CGIsCpG islands

MAQmapping and assembly with qualities

FDRFalse discovery rate

FWERfamilywise error rate

LINElong interspersed nuclear element

TSSstranscript start sites.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-10-223 contains supplementary material, which is available to authorized users.

Jian Li, Fei Gao, Ning Li contributed equally to this work.

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Autor: Jian Li - Fei Gao - Ning Li - Shengting Li - Guangliang Yin - Geng Tian - Shangang Jia - Kai Wang - Xiuqing Zhang - Huanm


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