cpg island methylation in human lymphocytes is highly correlated with dna sequence, repeats, and predicted dna structurecpg岛人类淋巴细胞是高度甲基化与dna序列,重复,并预测dna结构.pdfVIP

CpG Island Methylation in Human Lymphocytes Is Highly Correlated with DNA Sequence, Repeats, and Predicted DNA Structure 1* 2 2 2 1 ¨ 2 Christoph Bock , Martina Paulsen , Sascha Tierling , Thomas Mikeska , Thomas Lengauer , Jorn Walter ¨ ¨ ¨ ¨ 1 Max-Planck-Institut fur Informatik, Saarbrucken, Germany, 2 Universitat des Saarlandes, Genetik/Epigenetik, Saarbrucken, Germany CpG island methylation plays an important role in epigenetic gene control during mammalian development and is frequently altered in disease situations such as cancer. The majority of CpG islands is normally unmethylated, but a sizeable fraction is prone to become methylated in various cell types and pathological situations. The goal of this study is to show that a computational epigenetics approach can discriminate between CpG islands that are prone to methylation from those that remain unmethylated. We develop a bioinformatics scoring and prediction method on the basis of a set of 1,184 DNA attributes, which refer to sequence, repeats, predicted structure, CpG islands, genes, predicted binding sites, conservation, and single nucleotide polymorphisms. These attributes are scored on 132 CpG islands across the entire human Chromosome 21, whose methylation status was previously established for normal human lymphocytes. Our results show that three groups of DNA attributes, namely certain sequence patterns, specific DNA repeats, and a particular DNA structure, are each highly correlated with CpG island methylation (correlation coefficients of 0.64, 0.66, and 0.49, respectively). We predicted, and subsequently experimentally examined 12 CpG islands from hu