Abstract
Aberrant DNA methylation of CpG islands, CpG island shores and first exons is known to play a key role in the altered gene expression patterns in all human cancers. To date, a systematic study on the effect of DNA methylation on gene expression using high resolution data has not been reported. In this study, we conducted an integrated analysis of MethylCap-sequencing data and Affymetrix gene expression microarray data for 30 breast cancer cell lines representing different breast tumor phenotypes. As well-developed methods for the integrated analysis do not currently exist, we created a series of four different analysis methods. On the computational side, our goal is to develop methylome data analysis protocols for the integrated analysis of DNA methylation and gene expression data on the genome scale. On the cancer biology side, we present comprehensive genome-wide methylome analysis results for differentially methylated regions and their potential effect on gene expression in 30 breast cancer cell lines representing three molecular phenotypes, luminal, basal A and basal B. Our integrated analysis demonstrates that methylation status of different genomic regions may play a key role in establishing transcriptional patterns in molecular subtypes of human breast cancer.
Highlights
The addition of a methyl group to cytosine residues in the context of CpG dinucleotides (i.e. 5-methylcytosine) by the DNA methyltransferease enzymes is the most well-studied epigenetic event
(4) To investigate relationship between transcription factors (TFs) and DNA methylation in promoter regions, we examined the relationship between DNA methylation at TFbinding sites (TFBS) and gene expression in the breast cancer molecular subtypes
We observe that the number of highly methylated (>50) promoter regions tended to be lower in basal B (BaB)
Summary
The addition of a methyl group to cytosine residues in the context of CpG dinucleotides (i.e. 5-methylcytosine) by the DNA methyltransferease enzymes is the most well-studied epigenetic event. DNA methylation is known to play significant roles in many cellular processes, including embryonic development, genomic imprinting, X-chromosome inactivation and preservation of chromosome stability. Aberrant DNA methylation has been shown to disrupt many cellular processes and is frequently observed in most human diseases, including cancer [1,2,3,4]. The effect of DNA methylation on tumor suppressor genes (TSGs) has been extensively studied [6]. Transcriptional silencing of this key class of genes could contribute to defective
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