Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells

Qing Xue*, Yang Xu, Huixia Yang, Lei Zhang, Jing Shang, Cheng Zeng, Ping Yin, Serdar E. Bulun

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)395-400
Number of pages6
JournalReproductive Sciences
Volume21
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • CpG island
  • DNA methylation
  • SF-1
  • endometriosis
  • intron

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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