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


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Article Info

DATE

2011-01-04

AUTHORS

Leda Mirbahai, Timothy D Williams, Huiqing Zhan, Zhiyuan Gong, J Kevin Chipman

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. More... »

PAGES

3-3

References to SciGraph publications

  • 2004-05. Epigenetics in human disease and prospects for epigenetic therapy in NATURE
  • 2006-08-04. Zebrafish promoter microarrays identify actively transcribed embryonic genes in GENOME BIOLOGY
  • 2010-02-18. High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma in MOLECULAR GENETICS AND GENOMICS
  • 2006-11-26. Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription in NATURE GENETICS
  • 1999-10. Absence of genome-wide changes in DNA methylation during development of the zebrafish in NATURE GENETICS
  • 2010-01-06. Transgenic Expression of Walleye Dermal Sarcoma Virus rv-cyclin Gene in Zebrafish and Its Suppressive Effect on Liver Tumor Development After Carcinogen Treatment in MARINE BIOTECHNOLOGY
  • 2007-04-03. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio in CANCER CELL INTERNATIONAL
  • 2005-12-04. Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression in NATURE BIOTECHNOLOGY
  • 2009-02-17. The context and potential of epigenetics in oncology in BRITISH JOURNAL OF CANCER
  • 2008-06. DNA methylation landscapes: provocative insights from epigenomics in NATURE REVIEWS GENETICS
  • 2005-07-10. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells in NATURE GENETICS
  • 2004-07-29. Global changes in genomic methylation levels during early development of the zebrafish embryo in DEVELOPMENT GENES AND EVOLUTION
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1471-2164-12-3

    DOI

    http://dx.doi.org/10.1186/1471-2164-12-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1015713870

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21205313


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