title: Comprehensive profiling of zebrafish hepatic proximal promoter CpG island methylation and its modification during chemical carcinogenesis.
abstract: BACKGROUND
  DNA methylation is an epigenetic mechanism associated with regulation of gene expression and it is modulated during chemical carcinogenesis. The zebrafish is increasingly employed as a human disease model; however there is a lack of information on DNA methylation in zebrafish and during fish tumorigenesis.
  
  
  RESULTS
  A novel CpG island tiling array containing 44,000 probes, in combination with immunoprecipitation of methylated DNA, was used to achieve the first comprehensive methylation profiling of normal adult zebrafish liver. DNA methylation alterations were detected in zebrafish liver tumors induced by the environmental carcinogen 7, 12-dimethylbenz(a)anthracene. Genes significantly hypomethylated in tumors were associated particularly with proliferation, glycolysis, transcription, cell cycle, apoptosis, growth and metastasis. Hypermethylated genes included those associated with anti-angiogenesis and cellular adhesion. Of 49 genes that were altered in expression within tumors, and which also had appropriate CpG islands and were co-represented on the tiling array, approximately 45% showed significant changes in both gene expression and methylation.
  
  
  CONCLUSIONS
  The functional pathways containing differentially methylated genes in zebrafish hepatocellular carcinoma have also been reported to be aberrantly methylated during tumorigenesis in humans. These findings increase the confidence in the use of zebrafish as a model for human cancer in addition to providing the first comprehensive mapping of DNA methylation in the normal adult zebrafish liver.
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. lxm701@bham.ac.uk
authors.forename: Leda
authors.initials: L
authors.lastname: Mirbahai
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Williams
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhan
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gong
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Chipman
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced*; D018899:CpG Islands; D019175:DNA Methylation; D004195:Disease Models, Animal; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D008099:Liver / Q000502:physiology*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015027:Zebrafish / Q000235:genetics*
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene