Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation

PLoS One. 2008 Sep 11;3(9):e3189. doi: 10.1371/journal.pone.0003189.

Abstract

Epigenetic changes are thought to lead to alterations in the property of cells, such as differentiation potential. Neural precursor cells (NPCs) differentiate only into neurons in the midgestational brain, yet they become able to generate astrocytes in the late stage of development. This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100beta, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown. Here we analyzed DNA methylation changes in mouse NPCs between the mid-(E11.5) and late (E14.5) stage of development by a genome-wide DNA methylation profiling method using microarrays and found that many astrocytic genes are demethylated in late-stage NPCs, enabling the cell to become competent to express these genes. Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes. Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Binding Sites
  • Cell Differentiation
  • DNA Methylation
  • Epigenesis, Genetic
  • Gene Expression Profiling*
  • Genome
  • Glial Fibrillary Acidic Protein / metabolism
  • Mice
  • Mice, Inbred ICR
  • Nerve Growth Factors / metabolism
  • Neurons / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / metabolism
  • Time Factors

Substances

  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins