Synergistic chromatin repression of the tumor suppressor gene RARB in human prostate cancers.
DNA methylation and polycomb proteins are well-known mediators of epigenetic silencing in mammalian cells. Usually described as mutually exclusive, this statement is today controversial and recent in vitro studies suggest the co-existence of both repressor systems. We addressed this issue in the study of Retinoic Acid Receptor β (RARβ), a tumor suppressor gene frequently silenced in prostate cancer. We found that the RARβ promoter is hypermethylated in all studied prostate tumors and methylation levels are positively correlated with H3K27me3 enrichments. Thus, by using bisulfite conversion and pyrosequencing of immunoprecipitated H3K27me3 chromatin, we demonstrated that DNA methylation and polycomb repression co-exist in vivo at this locus. We found this repressive association in 6/6 patient tumor samples of different Gleason score, suggesting a strong interplay of DNA methylation and EZH2 to silence RARβ during prostate tumorigenesis.
['Moison|Céline|C|', 'Assemat|Fanny|F|', 'Daunay|Antoine|A|', 'Tost|Jörg|J|', 'Guieysse-Peugeot|Anne-Laure|AL|', 'Arimondo|Paola B|PB|']
D000368:Aged D002843:Chromatin D018899:CpG Islands D019175:DNA Methylation D016147:Genes, Tumor Suppressor D006657:Histones D006801:Humans D008297:Male D008875:Middle Aged D011401:Promoter Regions, Genetic D011471:Prostatic Neoplasms D018168:Receptors, Retinoic Acid
prostate cancer polycomb protein EZH2 DNA hypermethylation H3K27 trimethylation retinoic acid receptor beta (RARβ)