Department of Urology, Heinrich Heine University, 40225 Düsseldorf, Germany.
Cancer Genomics Proteomics. 2010 Mar-Apr;7(2):51-60.
Imprinted genes are often arranged in clusters epigenetically controlled by differentially methylated regions (DMR) containing bivalent histone modifications. Both DNA hypermethylation and hypomethylation in cancer can therefore disturb imprinted gene expression. We have studied expression, DNA methylation and histone modifications of TFPI2, a presumed tumor suppressor, and that of other genes in the 7q21 imprinted gene cluster in prostate cancer.
TFPI, TFPI2, SGCE and PON2 expression were assessed by qRT-PCR in prostate cancer tissues and cell lines. DNA methylation and histone modifications were investigated by bisulphite sequencing and chromatin immunoprecipatation.
TFPI2 was highly variably expressed in cancer tissues, in contrast to TFPI, and did not correlate to unchanged SGCE and significantly elevated PON2 expression. TFPI2 expression variations were unrelated to global DNA hypomethylation, but were associated with promoter methylation. PC3 cells with high expression retained normal methylation and bivalent histone modifications at DMR and promoter, whereas low-expressing LNCaP cells presented aberrant DNA methylation and more repressive histone modifications.
Epigenetic disturbances in the 7q21 cluster affect imprinted genes in a non-coordinate manner suggesting an unstable epigenetic state prone to selection for specific expression changes.
印迹基因通常通过含有二价组蛋白修饰的差异甲基化区域（DMR）进行表观遗传控制，形成簇状排列。因此，癌症中的 DNA 高甲基化和低甲基化都可能干扰印迹基因的表达。我们研究了前列腺癌中 7q21 印迹基因簇中假定的肿瘤抑制因子 TFPI2 以及其他基因的表达、DNA 甲基化和组蛋白修饰。
通过 qRT-PCR 评估前列腺癌组织和细胞系中 TFPI、TFPI2、SGCE 和 PON2 的表达。通过亚硫酸氢盐测序和染色质免疫沉淀研究 DNA 甲基化和组蛋白修饰。
TFPI2 在癌症组织中的表达高度可变，与 TFPI 相反，与不变的 SGCE 和显著升高的 PON2 表达无关。TFPI2 表达变化与全局 DNA 低甲基化无关，但与启动子甲基化有关。高表达的 PC3 细胞在 DMR 和启动子处保留正常的甲基化和二价组蛋白修饰，而低表达的 LNCaP 细胞则表现出异常的 DNA 甲基化和更具抑制性的组蛋白修饰。
7q21 簇中的表观遗传干扰以非协调的方式影响印迹基因，表明不稳定的表观遗传状态容易选择特定的表达变化。
