Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis
Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis
复制标题
从外显子 II 到内含子 III 的 CpG 岛的高甲基化与子宫内膜异位症基质细胞中类固醇生成因子 1 的表达相关
DOI：
10.1177/1933719111404614
复制
发表时间：
2011-11-01
影响因子：
2.9
通讯作者：
Bulun, Serdar E.
中科院分区：
文献类型：
--
作者：
Xue, Qing;Zhou, Ying Fang;Bulun, Serdar E.
子宫内膜异位症是一种雌激素依赖性疾病。类固醇生成因子1（SF-1）是一种转录因子，在乳腺癌来源的基质细胞中激活多种类固醇生成基因以进行雌激素生物合成是必不可少的。目的：探讨SF-1在子宫内膜和子宫内膜异位症间质细胞中差异表达的机制。设计：我们在SF-1基因中发现了一个新的CpG岛，从外显子II到内含子III。我们评估了这个CpG岛的甲基化状态。患者：来自无病受试者的在位子宫内膜（n = 8）和卵巢囊性子宫内膜异位症病变壁（n = 8）。所有患者均未接受任何术前激素治疗。从这两种类型的组织中分离基质细胞。结果：子宫内膜异位症间质细胞SF-1 mRNA水平明显高于子宫内膜间质细胞。亚硫酸氢盐测序显示，与子宫内膜细胞相比，子宫内膜癌细胞的甲基化显著增加（P <0.001）。观察到mRNA水平与外显子II/内含子III甲基化百分比之间的强相关性。具体来说，这种关联的Pearson相关系数为0.98（P <0.001）。结论：我们证明了SF-1基因编码外显子/内含子序列的甲基化正调控其在子宫内膜异位症中的表达，而其在正常子宫内膜中的低甲基化与SF-1水平显著降低相关。
Endometriosis is an estrogen-dependent disease. Steroidogenic factor 1 (SF-1), a transcription factor, is essential for the activation of multiple steroidogenic genes for estrogen biosynthesis in endometriosis-derived stromal cells. Objective: Unravel the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells. DESIGN: We identified a novel CpG island in the SF-1 gene, which spans from exon II to intron III. We evaluated the methylation status of this CpG island. PATIENTS: Eutopic endometrium from disease-free participants (n = 8) and the walls of cystic endometriosis lesions of the ovaries (n = 8). None of the patients had received any preoperative hormonal therapy. Stromal cells were isolated from these 2 types of tissues. Results: SF-1 messenger RNA (mRNA) levels in endometriotic stromal cells were significantly higher than those in endometrial stromal cells. Bisulfite sequencing showed strikingly increased methylation in endometriotic cells compared with endometrial cells (P < .001). A strong correlation between mRNA levels and percentage methylation of the exon II/intron III are observed. Specifically, the Pearson correlation coefficient was .98 (P < .001) for this association. Conclusions: We demonstrated that methylation of a coding exon/intron sequence in the SF-1 gene positively regulated its expression in endometriosis, whereas its hypomethylation in normal endometrium was associated with drastically lower SF-1 levels.