Enriched Transcription Factor Binding Sites in Hypermethylated Gene Promoters in Drug Resistant Cancer Cells. Export

@article{citeulike:2881825, abstract = {MOTIVATION: In the human genome, "CpG islands", CG-rich region 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 databases to globally analyze sequences methylated in a laboratory model for the development of drug-resistant cancer. Our results demonstrated that four transcription factor binding sites (TFBS) were enriched in hyper-methylated sequences. More interestingly, over-representation 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. CONTACT: sunkim2@indiana.edu, knephew@indiana.edu.}, address = {Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, USA Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, USA School of Informatics, Indiana University, Bloomington, IN 47408, USA School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea Department of Biostatistics, Department of Cellular and Integrative Physiology, IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, USA Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA.}, author = {Li, Meng and Paik, Hyun-Il Henry I. and Balch, Curt and Kim, Yoosung and Li, Lang and Huang, Tim H-M H. and Nephew, Kenneth P P. and Kim, Sun}, citeulike-article-id = {2881825}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/bioinformatics/btn256}, citeulike-linkout-1 = {http://bioinformatics.oxfordjournals.org/cgi/content/abstract/24/16/1745}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18540022}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18540022}, day = {6}, doi = {10.1093/bioinformatics/btn256}, issn = {1460-2059}, journal = {Bioinformatics (Oxford, England)}, keywords = {cancer, dna\_modification, transcription\_factor}, month = {June}, posted-at = {2008-06-11 08:41:34}, priority = {2}, title = {Enriched Transcription Factor Binding Sites in Hypermethylated Gene Promoters in Drug Resistant Cancer Cells.}, url = {http://dx.doi.org/10.1093/bioinformatics/btn256}, year = {2008} }

TY - JOUR ID - citeulike:2881825 L3 - citeulike-article-id:2881825 N2 - MOTIVATION: In the human genome, "CpG islands", CG-rich region 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 databases to globally analyze sequences methylated in a laboratory model for the development of drug-resistant cancer. Our results demonstrated that four transcription factor binding sites (TFBS) were enriched in hyper-methylated sequences. More interestingly, over-representation 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. CONTACT: sunkim2@indiana.edu, knephew@indiana.edu. JF - Bioinformatics (Oxford, England) SN - 1460-2059 AD - Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, USA Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, USA School of Informatics, Indiana University, Bloomington, IN 47408, USA School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea Department of Biostatistics, Department of Cellular and Integrative Physiology, IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, USA Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA. TI - Enriched Transcription Factor Binding Sites in Hypermethylated Gene Promoters in Drug Resistant Cancer Cells. KW - cancer KW - dna_modification KW - transcription_factor AU - Li, Meng AU - Paik, Hyun-Il Henry AU - Balch, Curt AU - Kim, Yoosung AU - Li, Lang AU - Huang, Tim H-M AU - Nephew, Kenneth P AU - Kim, Sun PY - 2008/06/06/ UR - http://dx.doi.org/10.1093/bioinformatics/btn256 ER -