Inhibition of maintenance DNA methylation by Stella

Biochem Biophys Res Commun. 2014 Oct 24;453(3):455-60. doi: 10.1016/j.bbrc.2014.09.101. Epub 2014 Oct 1.

Abstract

DNA methylation is a key epigenetic regulator in mammals, and the dynamic balance between methylation and demethylation impacts various processes, from development to disease. DNA methylation is erased during replication when DNA methyltransferase 1 (DNMT1) fails to methylate the daughter strand, in a process known as passive DNA demethylation. We found that the enforced expression of Stella (also known as PGC7, Dppa3), a maternal factor required for the maintenance of DNA methylation in early embryos, induced global DNA demethylation in NIH3T3 cells. This demethylation was caused by the binding of Stella to Np95 (also known as Uhrf1, ICBP90) and the subsequent inhibition of DNMT1 recruitment. Considering that impaired DNA methylation profiles are associated with various developmental or disease phenomena, Stella may be a powerful tool with which to study the biological effects of global DNA hypomethylation.

Keywords: DNA demethylation; Dnmt1; Np95; Stella.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone
  • DNA Methylation / physiology*
  • HEK293 Cells
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Proteins / physiology*
  • Two-Hybrid System Techniques

Substances

  • Chromosomal Proteins, Non-Histone
  • DPPA3 protein, human
  • Proteins