title: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: The Gade Institute, University of Bergen, Bergen, Norway. Xisong.Ke@gades.uib.no
authors.forename: Xi-Song
authors.initials: XS
authors.lastname: Ke
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Kari
authors.initials: K
authors.lastname: Rostad
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Li
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
authors.forename: Ole Johan
authors.initials: OJ
authors.lastname: Halvorsen
authors.forename: Svein A
authors.initials: SA
authors.lastname: Haukaas
authors.forename: Inge
authors.initials: I
authors.lastname: Jonassen
authors.forename: Kjell
authors.initials: K
authors.lastname: Petersen
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldfinger
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Anne M
authors.initials: AM
authors.lastname: Oyan
authors.forename: Karl-Henning
authors.initials: KH
authors.lastname: Kalland
mesh_terms: D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006657:Histones / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*
chemical_list: D006657:Histones; D035683:MicroRNAs; D008239:Lysine