UNLABELLED: Steroidogenic factor 1 (SF-1), a transcriptional factor essential for estrogen biosynthesis, is undetectable in endometrial stromal cells and aberrantly expressed in endometriotic stromal cells. OBJECTIVE: We tried to gain further insight into the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells. DESIGN: We had previously identified a novel CpG island in SF-1, which is located in the downstream intron 1 region. Here, we evaluated the methylation status of this CpG island. PATIENTS: We obtained the eutopic endometrium from disease-free participants (n = 8) and the walls of cystic endometriosis lesions of the ovaries from another group of participants (n = 8). None of the patients had received any preoperative hormonal therapy. INTERVENTIONS: Stromal cells were isolated from these 2 types of tissues and subjected to DNA bisulfite treatment and sequence analysis. RESULTS: The 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 of a 1-kbp region around the previously identified CpG island in endometriotic cells compared with endometrial cells (P < .001). A strong correlation between SF-1 mRNA levels and percentage methylation of the intron 1 region of the SF-1 gene was observed in endometriotic cells (Spearman correlation coefficient, .96; P < .001). CONCLUSIONS: Methylation of the intron 1 region of the SF-1 gene is associated with its expression in endometriotic cells. This CpG island therefore plays an important role in regulating SF-1 expression.
UNLABELLED: Steroidogenic factor 1 (SF-1), a transcriptional factor essential for estrogen biosynthesis, is undetectable in endometrial stromal cells and aberrantly expressed in endometriotic stromal cells. OBJECTIVE: We tried to gain further insight into the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells. DESIGN: We had previously identified a novel CpG island in SF-1, which is located in the downstream intron 1 region. Here, we evaluated the methylation status of this CpG island. PATIENTS: We obtained the eutopic endometrium from disease-free participants (n = 8) and the walls of cystic endometriosis lesions of the ovaries from another group of participants (n = 8). None of the patients had received any preoperative hormonal therapy. INTERVENTIONS: Stromal cells were isolated from these 2 types of tissues and subjected to DNA bisulfite treatment and sequence analysis. RESULTS: The 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 of a 1-kbp region around the previously identified CpG island in endometriotic cells compared with endometrial cells (P < .001). A strong correlation between SF-1 mRNA levels and percentage methylation of the intron 1 region of the SF-1 gene was observed in endometriotic cells (Spearman correlation coefficient, .96; P < .001). CONCLUSIONS: Methylation of the intron 1 region of the SF-1 gene is associated with its expression in endometriotic cells. This CpG island therefore plays an important role in regulating SF-1 expression.
Entities:
Keywords:
CpG island; DNA methylation; SF-1; endometriosis; intron
Authors: Matthew T Dyson; Toshiyuki Kakinuma; Mary Ellen Pavone; Diana Monsivais; Antonia Navarro; Saurabh S Malpani; Masanori Ono; Serdar E Bulun Journal: Fertil Steril Date: 2015-08-01 Impact factor: 7.329
Authors: Matthew T Dyson; Damian Roqueiro; Diana Monsivais; C Mutlu Ercan; Mary Ellen Pavone; David C Brooks; Toshiyuki Kakinuma; Masanori Ono; Nadereh Jafari; Yang Dai; Serdar E Bulun Journal: PLoS Genet Date: 2014-03-06 Impact factor: 5.917