DNA Methylation Is a Critical Cell-Intrinsic Determinant of Astrocyte Differentiation in the Fetal Brain

Takumi Takizawa, Kinichi Nakashima, Masakazu Namihira, Wataru Ochiai, Atsumi Uemura, Makoto Yanagisawa, Naoyuki Fujita, Mitsuyoshi Nakao, Tetsuya Taga

Research output: Contribution to journalArticle

442 Citations (Scopus)

Abstract

Astrocyte differentiation, which occurs late in brain development, is largely dependent on the activation of a transcription factor, STAT3. We show that astrocytes, as judged by glial fibrillary acidic protein (GFAP) expression, never emerge from neuroepithelial cells on embryonic day (E) 11.5 even when STAT3 is activated, in contrast to E14.5 neuroepithelial cells. A CpG dinucleotide within a STAT3 binding element in the GFAP promoter is highly methylated in E11.5 neuroepithelial cells, but is demethylated in cells responsive to the STAT3 activation signal to express GFAP. This CpG methylation leads to inaccessibility of STAT3 to the binding element. We suggest that methylation of a cell type-specific gene promoter is a pivotal event in regulating lineage specification in the developing brain.

Original languageEnglish
Pages (from-to)749-758
Number of pages10
JournalDevelopmental Cell
Volume1
Issue number6
DOIs
Publication statusPublished - Dec 1 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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