UNLABELLED: 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.
UNLABELLED: 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.
Authors: Yan Y Sanders; Namasivayam Ambalavanan; Brian Halloran; Xiangyu Zhang; Hui Liu; David K Crossman; Molly Bray; Kui Zhang; Victor J Thannickal; James S Hagood Journal: Am J Respir Crit Care Med Date: 2012-06-14 Impact factor: 21.405
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: Antonia Navarro; Ping Yin; Diana Monsivais; Simon M Lin; Pan Du; Jian-Jun Wei; Serdar E Bulun Journal: PLoS One Date: 2012-03-13 Impact factor: 3.240
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
Authors: Emma N Bermingham; Shalome A Bassett; Wayne Young; Nicole C Roy; Warren C McNabb; Janine M Cooney; Di T Brewster; William A Laing; Matthew P G Barnett Journal: BMC Med Genomics Date: 2013-03-05 Impact factor: 3.063