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Sirt2 epigenetically down-regulates PDGFRα expression and promotes CG4 cell differentiation

Na Fang1,2, Junjun Cheng1, Chu Zhang1

  • 1a Department of Biochemistry and Molecular Biology , Basic Medical School, Henan University , Kaifeng , China.

Cell Cycle (Georgetown, Tex.)
|April 26, 2019
PubMed

Insights

Sirtuin 2 (Sirt2) aids oligodendroglial cell differentiation by epigenetically suppressing PDGFRα expression, promoting a shift from proliferation to a post-mitotic state.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Epigenetics

Background:

  • Sirtuin 2 (Sirt2) enhances cellular processes and myelin basic protein (MBP) expression in CG4 cells.
  • The precise mechanism by which Sirt2 promotes oligodendroglial differentiation was previously unclear.
  • Sirt2 expression in CG4 cells is known to be suppressed by the transcription factor Nkx2.2.

Purpose of the Study:

  • To elucidate the detailed mechanism of Sirt2 in facilitating oligodendroglial cell differentiation.
  • To investigate the role of Sirt2 in regulating PDGFRα expression and its impact on CG4 cell proliferation and differentiation.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) assay to detect Sirt2 binding to the PDGFRα promoter.
  • Bisulfite sequencing to assess DNA methylation at the PDGFRα promoter.
  • Sirt2 and PDGFRα knockdown/overexpression experiments.
  • Cell proliferation assays.

Main Results:

  • Sirt2 translocates into the nucleus during CG4 cell differentiation induction.
  • Sirt2 binds to the PDGFRα promoter, inducing DNA methylation and histone H3 K27 trimethylation, thereby suppressing gene transcription.
  • Sirt2 overexpression downregulates PDGFRα expression, while PDGFRα or Sirt2 knockdown affects cell proliferation.
  • Sirt2 facilitates CG4 cell differentiation by suppressing PDGFRα, promoting a transition from proliferation to a post-mitotic state.

Conclusions:

  • Sirt2 plays a critical role in CG4 cell differentiation through nuclear translocation and epigenetic modification of the PDGFRα promoter.
  • Suppression of PDGFRα expression by Sirt2 is a key mechanism driving CG4 cells from a proliferative progenitor state to a post-mitotic differentiated state.
Keywords:
PDGFRαSirt2differentiationoligodendrocyte

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