|Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5 ′ CpG island in endometriosis|
|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|
|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|
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.
|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
|Xue, Qing,Lin, Zhihong,Yin, Ping,et al. Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5 ′ CpG island in endometriosis[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2007,92(8):3261-3267.|
|APA||Xue, Qing.,Lin, Zhihong.,Yin, Ping.,Milad, Magdy P..,Cheng, You-Hong.,...&Bulun, Serdar E..(2007).Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5 ′ CpG island in endometriosis.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,92(8),3261-3267.|
|MLA||Xue, Qing,et al."Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5 ′ CpG island in endometriosis".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 92.8(2007):3261-3267.|