PUBLICATION

Comprehensive profiling of zebrafish hepatic proximal promoter CpG island methylation and its modification during chemical carcinogenesis

Authors
Mirbahai, L., Williams, T.D., Zhan, H., Gong, Z., and Chipman, J.K.
ID
ZDB-PUB-110110-25
Date
2011
Source
BMC Genomics   12: 3 (Journal)
Registered Authors
Gong, Zhiyuan, Zhan, Huiqing
Keywords
none
MeSH Terms
  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Carcinogens
  • Carcinoma, Hepatocellular/chemically induced*
  • CpG Islands
  • DNA Methylation*
  • Disease Models, Animal
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Liver/physiology*
  • Liver Neoplasms/chemically induced*
  • Liver Neoplasms/genetics*
  • Promoter Regions, Genetic*
  • Zebrafish/genetics*
PubMed
21205313 Full text @ BMC Genomics
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. CONCLUSION: 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping