title: Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues.
abstract: OBJECTIVE
  To search for the demethylated cytosine-phosphate-guanine (CpG) islands within the aromatase gene in stromal cells derived from endometriotic chocolate cysts.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Department of Obstetrics and Gynecology and Department of Biosignaling, Tottori University, Yonago, Japan.
  
  
  METHODS
  Twenty-eight women who underwent laparoscopy (n=14) and laparotomy (n=14).
  
  
  METHODS
  Endometrial and endometriotic stromal cells were obtained from the uterus and chocolate cyst lining of the ovary.
  
  
  METHODS
  We searched for the CpG island and examined methylation profile and the association of methyl-binding proteins with the CpG island.
  
  
  RESULTS
  Up-regulation of aromatase messenger RNA (mRNA) expression was demonstrated in endometriotic cells. Three proximal promoters drove the mRNA expression. In endometrial cells, a marginal level of aromatase mRNA expression was observed. Treating endometrial cells with the demethylating agent 5-aza-2'-deoxycytidine markedly enhanced aromatase mRNA expression. The same promoters as in the endometriotic cells were used. To identify the unmethylated CpGs in endometriotic cells, we searched for CpG islands within the aromatase gene and subsequently examined the methylation profiles. Sequence analysis of bisulfite-treated genomic DNA demonstrated a stretch of CpG demethylation within a nonpromoter CpG island of the aromatase gene in endometriotic cells. In endometrial cells, the CpG sequences were heavily methylated and associated with methyl-CpG-binding proteins.
  
  
  CONCLUSIONS
  The up-regulation of the aromatase gene in endometriosis may be ascribed to the epigenetic disorder associated with aberrant DNA demethylation in a nonpromoter CpG island.
authors.affiliation: Department of Biosignaling, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Izawa
authors.forename: Fuminori
authors.initials: F
authors.lastname: Taniguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Uegaki
authors.forename: Eri
authors.initials: E
authors.lastname: Takai
authors.forename: Tomio
authors.initials: T
authors.lastname: Iwabe
authors.forename: Naoki
authors.initials: N
authors.lastname: Terakawa
authors.forename: Tasuku
authors.initials: T
authors.lastname: Harada
mesh_terms: D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation / Q000502:physiology*; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D014599:Uterus / Q000201:enzymology / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D001141:Aromatase