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

研究成果: Contribution to journalArticle査読

443 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)749-758
ページ数10
ジャーナルDevelopmental Cell
1
6
DOI
出版ステータス出版済み - 12 1 2001
外部発表はい

All Science Journal Classification (ASJC) codes

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

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