Synergistic chromatin repression of the tumor suppressor gene RARB in human prostate cancers

被引：31

作者：

Moison, Celine ^{[1
,2
,3
,4
]}

Assemat, Fanny ^{[1
]}

Daunay, Antoine ^{[5
]}

Tost, Joerg ^{[5
,6
]}

Guieysse-Peugeot, Anne-Laure ^{[2
,3
]}

Arimondo, Paola B. ^{[1
]}

机构：

[1] CNRS Pierre Fabre, Epigenet Targeting Canc ETaC, Toulouse, France

[2] CNRS, MNHN, UMR7196, Paris, France

[3] INSERM, U565, Paris, France

[4] Univ Paris 06, Paris, France

[5] Fondat Jean Dausset, Lab Funct Genom, CEPH, Paris, France

[6] CEA Inst Genom, Ctr Natl Genotypage, Lab Epigenet & Environm, Evry, France

来源：

EPIGENETICS | 2014年 / 9卷 / 04期

关键词：

polycomb protein; EZH2; DNA hypermethylation; prostate cancer; retinoic acid receptor beta (RAR beta); H3K27; trimethylation; ACID RECEPTOR-BETA; POLYCOMB TARGET GENES; GROUP PROTEIN EZH2; DNA METHYLATION; BREAST-CANCER; MESENCHYMAL TRANSITION; CELLS; HYPERMETHYLATION; HISTONE; EXPRESSION;

D O I：

10.4161/epi.27869

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta (RAR beta), a tumor suppressor gene frequently silenced in prostate cancer. We found that the RAR beta 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 RAR beta during prostate tumorigenesis.

引用

页码：477 / 482

页数：6

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