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学科主题: 临床医学
题名:
Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5 ′ CpG island in endometriosis
作者: Xue, Qing; Lin, Zhihong; Yin, Ping; Milad, Magdy P.; Cheng, You-Hong; Confino, Edmond; Reierstad, Scott; Bulun, Serdar E.
刊名: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
发表日期: 2007-08-01
DOI: 10.1210/jc.2007-0494
卷: 92, 期:8, 页:3261-3267
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: DNA METHYLATION ; EPIGENETIC MODIFICATIONS ; AROMATASE EXPRESSION ; GENE-EXPRESSION ; KEY REGULATOR ; CANCER-CELLS ; E-BOX ; PROMOTER ; BINDING ; PROTEINS
英文摘要:

Context: Endometriosis is an estrogen-dependent disease. Steroidogenic factor-1 (SF-1), a transcriptional factor essential for activation of multiple steroidogenic genes for estrogen biosynthesis, is undetectable in normal endometrial stromal cells and aberrantly expressed in endometriotic stromal cells.

Objective: The objective of the study was to unravel the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells.

Design: We identified a CpG island flanking the SF-1 promoter and exon I region and determined its methylation patterns in endometrial and endometriotic cells.

Setting: The study was conducted at Northwestern University.

Patients or Other Participants: Eutopic endometrium from diseasefree subjects (n = 8) and the walls of cystic endometriosis lesions of the ovaries (n = 8) were investigated. Intervention(s): Stromal cells were isolated from these two types of tissues.

Main Outcome Measure(s): Measures are mentioned in Results.

Results: SF-1 mRNA and protein levels in endometriotic stromal cells were significantly higher than those in endometrial stromal cells (P < 0.001). Bisulfite sequencing showed strikingly increased methylation in endometrial cells, compared with endometriotic cells (P < 0.001). Demethylation by 5-aza-2(′)-deoxycytidine increased SF-1 mRNA levels by up to 55.48-fold in endometrial cell (P < 0.05). Luciferase assays showed that the -85/+239 region bearing the CpG island regulated its activity (P < 0.01). Natural or in vitro methylation of this region strikingly reduced SF-1 promoter activity in both cell types (P < 0.01). Chromatin immunoprecipitation assay showed that methyl-CpG-binding domain protein 2 binds to the SF-1 promoter in endometrial but not endometriotic cells.

Conclusions: This is the first demonstration of methylation-dependent regulation of SF-1 in any mammalian tissue. These findings point to a new mechanism for targeting local estrogen biosynthesis in endometriosis.

语种: 英语
WOS记录号: WOS:000248570600067
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62322
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Northwestern Univ, Feinberg Sch Med, Div Reprod Biol Res, Chicago, IL 60611 USA
2.Northwestern Univ, Feinberg Sch Med, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA
3.Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA
4.Peking Univ, First Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China

Recommended Citation:
Xue, Qing,Lin, Zhihong,Yin, Ping,et al. Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5 &prime; CpG island in endometriosis[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY &amp; METABOLISM,2007,92(8):3261-3267.
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