Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

ChIP-chip by array of zebra fish hepatocellular carcinoma and normal liver to detect differences in CG island methylation

ABSTRACT: The aim of the experiment was to detect differences in CG island methylation between hepatocellular carcinoma and normal liver in zebrafish. Zebrafish were treated with DMBA, producing hepatocellular carcinoma, genomic DNA was prepared from these and control zebrafish livers. Methylated DNA was immunoprecipitated from HCC and control samples and labeled with Cy5, samples were co-hybridised with Cy3 labeled zebrafish genomic DNA to the Birmingham D. rerio Agilent 025794 45220 v1 microarray.

ORGANISM(S): Danio rerio

DISEASE(S): normal

SUBMITTER: Tim Williams

PROVIDER: E-MTAB-209 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Mirbahai Leda L Williams Timothy D TD Zhan Huiqing H Gong Zhiyuan Z Chipman J Kevin JK

BMC genomics 20110104

<h4>Background</h4>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.<h4>Results</h4>A novel CpG island tiling array containing 44,000 probes, in combination with immunoprecipitation of methylated DNA, was used to achieve the first comprehensi ...[more]

PMID: 21205313

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Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness. DNA methylome analysis of pooled Human, Chimpanzee and Macaque

Dataset Information

ChIP-chip by array of zebra fish hepatocellular carcinoma and normal liver to detect differences in CG island methylation

Publications

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

Similar Datasets

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