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Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells

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dc.contributor.author Ke, Xi-Song
dc.contributor.author Qu, Yi
dc.contributor.author Cheng, Yang
dc.contributor.author Li, Wen-Cheng
dc.contributor.author Rotter, Varda
dc.contributor.author Øyan, Anne Margrete
dc.contributor.author Kalland, Karl-Henning
dc.date.accessioned 2011-04-08T07:09:27Z
dc.date.available 2011-04-08T07:09:27Z
dc.date.issued 2010-11-25
dc.identifier.citation BMC Genomics 11:669 en_US
dc.identifier.issn 1471-2164
dc.identifier.uri http://dx.doi.org/10.1186/1471-2164-11-669
dc.identifier.uri http://hdl.handle.net/1956/4637
dc.description.abstract Background Previously we reported extensive gene expression reprogramming during epithelial to mesenchymal transition (EMT) of primary prostate cells. Here we investigated the hypothesis that specific histone and DNA methylations are involved in coordination of gene expression during EMT. Results Genome-wide profiling of histone methylations (H3K4me3 and H3K27me3) and DNA methylation (DNAMe) was applied to three cell lines at different stages of a stepwise prostate cell model involving EMT and subsequent accumulation of malignant features. Integrated analyses of epigenetic promoter modifications and gene expression changes revealed strong correlations between the dynamic changes of histone methylations and gene expression. DNA methylation was weaker associated with global gene repression, but strongly correlated to gene silencing when genes co-modified by H3K4me3 were excluded. For genes labeled with multiple epigenetic marks in their promoters, the level of transcription was associated with the net signal intensity of the activating mark H3K4me3 minus the repressive marks H3K27me3 or DNAMe, indicating that the effect on gene expression of bivalent marks (H3K4/K27me3 or H3K4me3/DNAMe) depends on relative modification intensities. Sets of genes, including epithelial cell junction and EMT associated fibroblast growth factor receptor genes, showed corresponding changes concerning epigenetic modifications and gene expression during EMT. Conclusions This work presents the first blueprint of epigenetic modifications in an epithelial cell line and the progeny that underwent EMT and shows that specific histone methylations are extensively involved in gene expression reprogramming during EMT and subsequent accumulation of malignant features. The observation that transcription activity of bivalently marked genes depends on the relative labeling intensity of individual marks provides a new view of quantitative regulation of epigenetic modification. en_US
dc.language.iso eng en_US
dc.publisher BioMed Central en
dc.rights Copyright 2010 Ke et al; licensee BioMed Central Ltd. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Global profiling of histone and DNA methylation reveals epigenetic-based regulation of gene expression during epithelial to mesenchymal transition in prostate cells en_US
dc.type Peer reviewed en
dc.type Journal article en
dc.rightsHolder Ke et al. en_US
dc.type.version publishedVersion en_US
bora.cristinID 826661


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Copyright 2010 Ke et al; licensee BioMed Central Ltd. Except where otherwise noted, this item's license is described as Copyright 2010 Ke et al; licensee BioMed Central Ltd.

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