Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells

J Biol Chem. 2003 May 9;278(19):16675-82. doi: 10.1074/jbc.M211715200. Epub 2003 Feb 27.

Abstract

Histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones, regulating gene transcription. Decidualization is the progestin-induced differentiation of estrogen-primed endometrial stromal cells (ESCs), which is crucial for implantation and maintenance of pregnancy. We here show that trichostatin A (TSA), a specific HDAC inhibitor, enhances the up-regulation of decidualization markers such as insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin in a dose-dependent manner that is directed by 17beta-estradiol (E(2)) plus progesterone (P(4)) in cultured ESCs, but not glandular cells, both isolated from human endometrium. Morphological changes resembling decidual transformation were also augmented by co-addition of TSA. Acid urea triton gel analysis and immunoblot using acetylated histone type-specific antibodies demonstrated that treatment with E(2) plus P(4) significantly increased the levels of acetylated H3 and H4 whose increment was augmented by co-treatment with TSA. Chromatin immunoprecipitation assay revealed that treatment with E(2) plus P(4) increased the amount of proximal progesterone-responsive region of IGFBP-1 promoter associated with acetylated H4, which was dramatically enhanced by co-addition of TSA. Taken together, our results suggest that histone acetylation is deeply involved in differentiation of human ESCs and that TSA has a potential as an enhancer of decidualization through promotion of progesterone action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / antagonists & inhibitors
  • Acetyltransferases / metabolism
  • Cell Line
  • Decidua / cytology*
  • Decidua / drug effects
  • Decidua / physiology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Estradiol / pharmacology*
  • Female
  • Histone Acetyltransferases
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism
  • Histones / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Pregnancy
  • Progesterone / pharmacology*
  • Prolactin / metabolism
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Saccharomyces cerevisiae Proteins / metabolism
  • Stromal Cells / cytology
  • Stromal Cells / physiology
  • Up-Regulation / drug effects

Substances

  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • Hydroxamic Acids
  • Insulin-Like Growth Factor Binding Protein 1
  • Saccharomyces cerevisiae Proteins
  • trichostatin A
  • Progesterone
  • Estradiol
  • Prolactin
  • Acetyltransferases
  • Histone Acetyltransferases
  • Histone Deacetylases