CpG dinucleotide methylation of the CYP19 I.3/II promoter modulates cAMP-stimulated aromatase activity

Masashi Demura, Serdar E Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Aromatase expression varies in a tissue-specific manner and among individuals. Aromatase promoter I.3/II, regulated by a cAMP response element (CRE), is normally quiescent in human skin fibroblasts, whereas its hyperactivity may cause local or systemic estrogen excess. We describe the methylation status of 6 CpG dinucleotides within a 571-bp fragment of promoter I.3/II containing a CRE in cAMP-responsive (n = 1) or nonresponsive (n = 3) primary skin fibroblasts cultured from healthy volunteers. Four out of 6 CpG dinucleotides were unmethylated in cAMP-responsive fibroblasts, whereas all 6 CpG dinucleotides were hypermethylated in cAMP-nonresponsive fibroblasts. Basal and cAMP-stimulated aromatase activity and promoter I.3/II activation were significantly higher in the presence of unmethylated DNA. Furthermore, methylation at the CRE interfered with CREB binding. Thus, methylation of CpG dinucleotides within promoter I.3/II regulates aromatase expression and may be one source of inter-individual variability. Furthermore, abnormal methylation of the aromatase promoter may contribute to aromatase overexpression in breast cancer.

Original languageEnglish (US)
Pages (from-to)127-132
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume283
Issue number1-2
DOIs
StatePublished - Feb 13 2008

Keywords

  • Aromatase
  • CYP19
  • DNA Methylation
  • Epigenesis
  • Promoter I.3/II
  • cAMP response element

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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