[-腦-] Genome-wide profiling
PLoS One. 2009;4(3):e4687. Epub 2009 Mar 5.
標題：Genome-wide profiling of histone h3 lysine 4 and lysine 27 trimethylation
reveals an epigenetic signature in prostate carcinogenesis.
Abstract
BACKGROUND:
Increasing evidence implicates the critical roles of epigenetic regulation in
cancer. Very recent reports indicate that global gene silencing in cancer is
associated with specific epigenetic modifications. However, the relationship
between epigenetic switches and more dynamic patterns of gene activation and
repression has remained largely unknown.
METHODOLOGY/PRINCIPAL FINDINGS:
Genome-wide profiling of the trimethylation of histone H3 lysine 4 (H3K4me3)
and lysine 27 (H3K27me3) was performed using chromatin immunoprecipitation
coupled with whole genome promoter microarray (ChIP-chip) techniques.
Comparison of the ChIP-chip data and microarray gene expression data revealed
that loss and/or gain of H3K4me3 and/or H3K27me3 were strongly associated with
differential gene expression, including microRNA expression, between prostate
cancer and primary cells. The most common switches were gain or loss of
H3K27me3 coupled with low effect on gene expression. The least prevalent
switches were between H3K4me3 and H3K27me3 coupled with much higher fractions
of activated and silenced genes. Promoter patterns of H3K4me3 and H3K27me3
corresponded strongly with coordinated expression changes of regulatory gene
modules, such as HOX and microRNA genes, and structural gene modules, such as
desmosome and gap junction genes. A number of epigenetically switched oncogenes
and tumor suppressor genes were found overexpressed and underexpressed
accordingly in prostate cancer cells.
CONCLUSIONS/SIGNIFICANCE:
This work offers a dynamic picture of epigenetic switches in carcinogenesis and
contributes to an overall understanding of coordinated regulation of gene
expression in cancer. Our data indicate an H3K4me3/H3K27me3 epigenetic
signature of prostate carcinogenesis.
PMID: 19262738 [PubMed - indexed for MEDLINE]PMCID: PMC2650415Free PMC Article
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