Enriched transcription factor binding sites in hypermethylated gene promoters in drug resistant cancer cells

Abstract

Motivation: In the human genome, 'CpG islands', CG-rich regions located in or near gene promoters, are normally unmethylated. However, in cancer cells, CpG islands frequently gain methylation, resulting in silencing of growth-limiting tumor suppressor genes. To our knowledge, the potential relationship between CpG island hypermethylation, transcription factor (TF) binding in local promoter regions and transcriptional control has not been previously explored in a genome-wide context. Results: In this study, we utilized bioinformatics tools and TF binding site(TFBs) databases to globally analyze sequences methylated in a laboratory model for the development of drug-resistant cancer. Our results demonstrated that four TFBS were enriched in hypermethylated sequences. More interestingly, overrepresentation of these TFBS was observed in hyper-/hypo-methylated sequences where significant changes in methylation levels were observed in drug-resistant cancer cells. In summary, we believe that these findings offer a means to further explore the relationship between DNA methylation and gene expression in drug resistance and tumorigenesis. © The Author 2008. Published by Oxford University Press. All rights reserved.