title: Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells.
abstract: OBJECTIVE
  To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma.
  
  
  METHODS
  Basic science.
  
  
  METHODS
  University research center.
  
  
  METHODS
  Premenopausal women with or without endometriosis.
  
  
  METHODS
  Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP.
  
  
  METHODS
  Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation.
  
  
  RESULTS
  IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD.
  
  
  CONCLUSIONS
  The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones.
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address: m-dyson@northwestern.edu.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Dyson
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kakinuma
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Diana
authors.initials: D
authors.lastname: Monsivais
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Antonia
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Saurabh S
authors.initials: SS
authors.lastname: Malpani
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.affiliation: Division of Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics; D004715:Endometriosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008875:Middle Aged; D010049:Ovarian Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D014018:Tissue Distribution; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B
keywords: DNA methyltransferase; Endometriosis; decidualization; estrogen receptor; steroidogenic factor-1