Results
| PMID | 17519303 |
| Gene Name | NR5A1 |
| Condition | Endometriosis |
| Association |
Associated |
| Population size | 16 |
| Population details | 16 (8 eutopic endometrium from disease-free subjects, 8 cystic endometriosis lesions of the ovaries) |
| Sex | Female |
| Associated genes | SF-1 |
| Other associated phenotypes |
Endometriosis |
|
J Clin Endocrinol Metab. 2007 Aug;92(8):3261-7. Epub 2007 May 22. Xue, Qing| Lin, Zhihong| Yin, Ping| Milad, Magdy P| Cheng, You-Hong| Confino, Edmond| Reierstad, Scott| Bulun, Serdar E Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois 60611, USA. 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 disease-free 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. Mesh Terms: Aromatase/biosynthesis| Aromatase Inhibitors/pharmacology/therapeutic use| Azacitidine/analogs & derivatives/pharmacology/therapeutic use| Blotting, Western| Cells, Cultured| Chromatin/metabolism| CpG Islands/*genetics| DNA Methylation| Endometrio |
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