GENOME-WIDE ANALYSIS AND MODELING OF DNA METHYLATION SUSCEPTIBILITY IN 30 BREAST CANCER CELL LINES BY USING CpG FLANKING SEQUENCES

초록

DNA methylation is an epigenetic modification of DNA that adds a methyl group to cytosine. Aberrant DNA methylation in the CpG context is frequently observed in cancer cells and it is known that aberrant DNA methylation silences tumor repressor genes. However, the mechanism of DNA methylation is not well understood. A widely accepted hypothesis is that DNA methylation does not randomly occur and may be controlled by some instructive mechanisms. In this paper, we conducted an extensive study on this important question by using proprietary sequencing data from methyl-binding domain protein (MBD)-Cap ChIP sequencing experiments for 30 breast cancer cell lines. The goal of our study is to investigate difference in nucleotide composition around CpG sites, where high levels of methylation are observed, and use the information for modeling DNA methylation susceptibility. First, we observed that DNA methylation is not uniform in the whole-genome region and also that the character composition of CpG flanking sequences are significantly different between hyper- and hypo-methylated groups. In an in-depth study, we used information theoretic approaches such as entropy and relative entropy to delineate character composition features and found enrichment of A (Adenine) and T (Thymine) in specific positions around hyper- methy

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