title: Genome-wide profiling of DNA methylation in human cancer cells.
abstract: Global changes in DNA methylation correlate with altered gene expression and genomic instability in cancer. We have developed a methylation-specific digital sequencing (MSDS) method that can assess DNA methylation on a genomic scale. MSDS is a simple, low-cost method that combines the use of methylation-sensitive restriction enzymes with second generation sequencing technology. DNA methylation in two colon cancer cell lines, HT29 and HCT116, was measured using MSDS. When methylation levels were compared between the two cell lines, many differentially methylated regions (DMRs) were identified in CpG island shore regions (located within 2kb of a CpG island), gene body regions and intergenic regions. The number of DMRs in the vicinity of gene transcription start sites correlated with the level of expression of TACC1, CLDN1, and PLEKHC1 (FERMT2) genes, which have been linked to carcinogenesis. The MSDS method has the potential to provide novel insight into the functional complexity of the human genome.
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. oisho@m.u-tokyo.ac.jp
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ogoshi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Oshima
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004262:DNA Restriction Enzymes / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D042822:Genomic Instability; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D024363:Transcription Initiation Site
chemical_list: D004262:DNA Restriction Enzymes