School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332, USA.
Front Biosci (Landmark Ed). 2012 Jan 1;17(2):396-406. doi: 10.2741/3934.
H1 linker histones play a key role in facilitating higher order chromatin folding. Emerging evidence suggests that H1 and its multiple variants are important epigenetic factors in modulating chromatin function and gene expression. Ovarian cancer is a devastating disease, ranking the fifth leading cause of all women cancer death due to its poor prognosis and difficulty in early diagnosis. Although epigenetic alterations in ovarian cancers are being appreciated in general, the role of H1 has not been explored. Here, using quantitative RT-PCR assays, we systematically examined the expression of 7 H1 genes in 33 human epithelial ovarian tumors. Whereas the expression of H1.3 was markedly increased, the expression of H10, H1.1, H1.4 and H1x were significantly reduced in malignant adenocarcinomas compared with benign adenomas. Strikingly, ovarian adenocarcinomas and adenomas exhibited characteristic expression patterns, and expression profiling of 7 H1 genes in tumor samples discriminated adenocarcinomas vs. adenomas with high accuracy. These findings indicate that the expression of H1 variants is exquisitely regulated and may serve as potential epigenetic biomarkers for ovarian cancer.
H1 连接组蛋白在促进高级染色质折叠中起着关键作用。新出现的证据表明,H1 及其多种变体是调节染色质功能和基因表达的重要表观遗传因素。卵巢癌是一种毁灭性疾病,由于预后不良和早期诊断困难,其死亡率在女性癌症中排名第五。尽管人们普遍认识到卵巢癌中的表观遗传改变,但 H1 的作用尚未得到探索。在这里,我们使用定量 RT-PCR 检测方法,系统地检测了 33 个人类上皮性卵巢肿瘤中 7 个 H1 基因的表达。与良性腺瘤相比,恶性腺癌中 H1.3 的表达明显增加,而 H10、H1.1、H1.4 和 H1x 的表达则显著降低。引人注目的是,卵巢腺癌和腺瘤表现出特征性的表达模式,并且肿瘤样本中 7 个 H1 基因的表达谱分析可以高度准确地区分腺癌和腺瘤。这些发现表明 H1 变体的表达受到精细调控,可能成为卵巢癌的潜在表观遗传生物标志物。