Methyl-CpG binding proteins are involved in restricting differentiation plasticity in neurons

Hiroki Setoguchi, Masakazu Namihira, Jun Kohyama, Hirotsugu Asano, Tsukasa Sanosaka, Kinichi Nakashima

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocytogenesis, which normally commences at later stages of development. We have previously reported that a particular cytosine residue within a STAT3-binding site in the astrocyte-specific marker glial fibrillary acidic protein (GFAP) gene promoter becomes demethylated in neuroepithelial cells as gestation proceeds. This demethylation correlates tightly with the onset of astrocyte differentiation, suggesting that a change in DNA methylation at cell-type-specific gene promoters controls the switch from neurogenesis to astrocytogenesis in the developing brain. Here, we show that late-gestation neuroepithelial cells, which have already lost the methylation in the STAT3-binding site within the GFAP promoter, can still give rise to neurons and that these neurons do not respond to a STAT3-activating cytokine to express GFAR Members of a transcriptional represser family, the methylated-CpG binding proteins (MBDs), including MeCP2, are predominantly expressed in neurons, and ectopic MeCP2 expression inhibited astrocyte differentiation of neuroepithelial cells. Moreover, we found that exon 1 of the GFAP gene remains hypermethylated even in neuroepithelial cells at a late developmental stage and in neurons differentiated from such neuroepithelial cells. We further demonstrate that MeCP2 actually binds to the highly methylated exon 1 of the GFAP gene in neurons. These results suggest that region-specific DNA methylation and MBDs play an important role in the regulation of differentiation plasticity in neurons.

Original languageEnglish
Pages (from-to)969-979
Number of pages11
JournalJournal of neuroscience research
Volume84
Issue number5
DOIs
Publication statusPublished - 2006 Oct 1
Externally publishedYes

Keywords

  • Epigenetics
  • MBD
  • Neural stem cell
  • Neuron
  • Plasticity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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