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; Confino, Edmond; Reierstad, Scott; Bulun, Serdar E.

doi:10.1210/jc.2007-0494

Cited by 182 publications

(162 citation statements)

References 38 publications

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“…We previously demonstrated that differential methylation of a CpG island at the promoter and exon I region regulates SF-1 transcriptional activity in endometriosis or endometrium-derived stromal cells. 16 This is consistent with a large body of literature showing that DNA methylation at the promoter region is generally associated with gene silencing.…”

Section: Discussionsupporting

confidence: 90%

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Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis

et al. 2011

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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 ¼ 8) and the walls of cystic endometriosis lesions of the ovaries (n ¼ 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.

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Section: Discussionsupporting

confidence: 90%

“…16 Here, we characterize another CpG island, this time, in the coding region of the gene. We identified an approximately 600-bp CpG island that spans from exon II to intron III.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis

et al. 2011

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“…Other studies highlighted a differential expression of the genes SF1 and estrogen receptor beta in endometriotic tissue compared with endometrium. Results indicated that expression was primarily controlled by a methylation-dependent epigenetic mechanism (5,6). In addition, various chromosomal aberrations have been reported in endometriotic samples and in ovarian carcinoma (7).…”

Section: Introductionmentioning

confidence: 99%

Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues

Forte

Schettino

Finicelli

et al. 2009

Mol Med

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Endometriosis is a chronic disease characterized by the presence of ectopic endometrial tissue outside of the uterus with mixed traits of benign and malignant pathology. In this study we analyzed in endometrial and endometriotic tissues the differential expression of a panel of genes that are involved in preservation of stemness status and consequently considered as markers of stem cell presence. The expression profiles of a panel of 13 genes (SOX2, SOX15, ERAS, SALL4, OCT4, NANOG, UTF1, DPPA2, BMI1, GDF3, ZFP42, KLF4, TCL1) were analyzed by reverse transcription-polymerase chain reaction in human endometriotic (n = 12) and endometrial samples (n = 14). The expression of SALL4 and OCT4 was further analyzed by immunohistochemical methods. Genes UTF1, TCL1, and ZFP42 showed a trend for higher frequency of expression in endometriosis than in endometrium (P < 0.05 for UTF1), whereas GDF3 showed a higher frequency of expression in endometrial samples. Immunohistochemical analysis revealed that SALL4 was expressed in endometriotic samples but not in endometrium samples, despite the expression of the corresponding mRNA in both the sample groups. This study highlights a differential expression of stemness-related genes in ectopic and eutopic endometrium and suggests a possible role of SALL4-positive cells in the pathogenesis of endometriosis.

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“…SF-1 is expressed in endometriotic cells whereas it is not usually detected in normal endometrium and can exert a role in the pathogenesis of endometriosis (Xue et al, 2007; reviewed in Bulun et al, 2009). SF-1 expression leads to an aberrant activation of StAR and CYP19 genes expression and to an increase of the endogenous synthesis of estrogen within endometriotic tissue, a key causative factor in the disease.…”

Section: Sf-1 Expression In Endometriosismentioning

confidence: 99%

NR5A1 (nuclear receptor subfamily 5, group A, member 1)

Ruggiero¹,

Doghman²,

Lalli³

2017

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Transcriptional Activation of Steroidogenic Factor-1 by Hypomethylation of the 5′ CpG Island in Endometriosis

Abstract: 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.

Cited by 182 publications

References 38 publications

Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis

Hypermethylation of the CpG Island Spanning From Exon II to Intron III is Associated With Steroidogenic Factor 1 Expression in Stromal Cells of Endometriosis

Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues

NR5A1 (nuclear receptor subfamily 5, group A, member 1)

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