{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:31:46Z","timestamp":1775932306239,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: In the human genome, \u2018CpG islands\u2019, 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.<\/jats:p><jats:p>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.<\/jats:p><jats:p>Contact: \u00a0sunkim2@indiana.edu; knephew@indiana.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn256","type":"journal-article","created":{"date-parts":[[2008,6,8]],"date-time":"2008-06-08T00:13:58Z","timestamp":1212884038000},"page":"1745-1748","source":"Crossref","is-referenced-by-count":10,"title":["Enriched transcription factor binding sites in hypermethylated gene promoters in drug resistant cancer cells"],"prefix":"10.1093","volume":"24","author":[{"given":"Meng","family":"Li","sequence":"first","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-il Henry","family":"Paik","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curt","family":"Balch","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoosung","family":"Kim","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lang","family":"Li","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim H-M.","family":"Huang","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth P.","family":"Nephew","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, USA"},{"name":"1 Medical Sciences, School of Medicine, Indiana University, Bloomington, IN 47404, 2Interdisciplinary Biochemistry Program, Indiana University, Bloomington, IN 47405, 3School of Informatics, Indiana University, Bloomington, IN 47408, 4IU Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN 46202, USA, 5School of Information and Communication Engineering, Inha University, Incheon 402-751, Korea, 6Department of Biostatistics, Indiana University, Indianapolis, IN 46202, 7Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, 8Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN 46202 and 9Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47404, 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