Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells

Matthew T. Dyson*, Toshiyuki Kakinuma, Mary Ellen Pavone, Diana Monsivais, Antonia Navarro, Saurabh S. Malpani, Masanori Ono, Serdar E. Bulun

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

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. Design Basic science. Setting University research center. Patient(s) Premenopausal women with or without endometriosis. Intervention(s) 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. Main Outcome Measure(s) 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. Result(s) 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. Conclusion(s) 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.

Original languageEnglish (US)
Pages (from-to)953-963.e2
JournalFertility and Sterility
Volume104
Issue number4
DOIs
StatePublished - Oct 1 2015

Keywords

  • DNA methyltransferase
  • Endometriosis
  • decidualization
  • estrogen receptor
  • steroidogenic factor-1

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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