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

Meng Li, Hyun Il Henry Paik, Curt Balch, Yoosung Kim, Lang Li, Hui-ming Huang, Kenneth P. Nephew, Sun Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1745-1748
Number of pages4
JournalBioinformatics
Volume24
Issue number16
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

CpG Islands
Transcription factors
Binding sites
Transcription Factor
Promoter
Cancer
Drugs
Transcription Factors
Genes
Binding Sites
Cells
Gene
Methylation
Cell
Genome
Pharmaceutical Preparations
Drug Resistance
Neoplasms
Human Genome
DNA Methylation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Computer Science Applications
  • Computational Theory and Mathematics

Cite this

Enriched transcription factor binding sites in hypermethylated gene promoters in drug resistant cancer cells. / Li, Meng; Paik, Hyun Il Henry; Balch, Curt; Kim, Yoosung; Li, Lang; Huang, Hui-ming; Nephew, Kenneth P.; Kim, Sun.

In: Bioinformatics, Vol. 24, No. 16, 08.2008, p. 1745-1748.

Research output: Contribution to journalArticle

Li, Meng ; Paik, Hyun Il Henry ; Balch, Curt ; Kim, Yoosung ; Li, Lang ; Huang, Hui-ming ; Nephew, Kenneth P. ; Kim, Sun. / Enriched transcription factor binding sites in hypermethylated gene promoters in drug resistant cancer cells. In: Bioinformatics. 2008 ; Vol. 24, No. 16. pp. 1745-1748.
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