MeCP2-mediated epigenetic regulation in senescent endothelial progenitor cells

Stem Cell Res Ther. 2018 Apr 3;9(1):87. doi: 10.1186/s13287-018-0828-y.

Abstract

Background: Cellular aging may be associated with epigenetics. Methyl-CpG-binding protein 2 (MeCP2) and sirtuin 1 (SIRT1) are two important epigenetic factors. Our former work demonstrated that MeCP2 expression increased and SIRT1 expression decreased in senescent endothelial progenitor cells (EPCs). This article aims to reveal the epigenetic regulation caused by MeCP2 in EPCs and discuss its mechanism.

Methods: Tube formation assay and cell apoptosis detection were used to evaluate the function of senescent EPCs induced by MeCP2 overexpression. Western blot analysis was used to testify the relative protein expression changed by MeCP2. Bisulfite sequencing methylation assay and chromatin immunoprecipitation assay were used to assess the degree of methylation and the relation of MeCP2 and SIRT1.

Results: MeCP2 reduced angiogenesis of senescent EPCs, promoted apoptosis, and caused senescent EPC dysfunction through SIRT1 promoter hypermethylation and histone modification.

Conclusions: MeCP2 mediated senescent EPC dysfunction through epigenetic regulation.

Keywords: Endothelial progenitor cells; Epigenetic; MeCP2; SIRT1; Senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence*
  • DNA Methylation
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism*
  • Endothelial Progenitor Cells / physiology
  • Epigenesis, Genetic*
  • Histone Code
  • Humans
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism

Substances

  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • SIRT1 protein, human
  • Sirtuin 1