17β-estradiol regulates the expression of apolipoprotein M through estrogen receptor α-specific binding motif in its promoter

Lipids Health Dis. 2017 Mar 31;16(1):66. doi: 10.1186/s12944-017-0458-x.

Abstract

Background: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression.

Results: Our results demonstrated either free 17β-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to -1575 bp (-GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region.

Conculsion: In summary, the present study indicates that 17β-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.

Keywords: Apolipoprotein M; Chromatin Immunoprecipitation (ChIP) assay; Electrophoretic mobility shift assay (EMSA); Estrogen receptor alpha; Estrogen responsive element.

MeSH terms

  • Apolipoproteins / genetics*
  • Apolipoproteins / metabolism
  • Apolipoproteins M
  • Base Sequence
  • Binding Sites
  • Estradiol / physiology*
  • Estrogen Receptor alpha / physiology*
  • Hep G2 Cells
  • Humans
  • Lipocalins / genetics*
  • Lipocalins / metabolism
  • MCF-7 Cells
  • Promoter Regions, Genetic
  • Protein Binding
  • Sequence Analysis, DNA
  • Transcriptional Activation*
  • Up-Regulation

Substances

  • APOM protein, human
  • Apolipoproteins
  • Apolipoproteins M
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Lipocalins
  • Estradiol