DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling

Guoping Fan, Keri Martinowich, Mark H. Chin, Fei He, Shaun D. Fouse, Leah Hutnick, Daisuke Hattori, Weihong Ge, Yin Shen, Hao Wu, Johanna ten Hoeve, Ke Shuai, Yi E. Sun

Research output: Contribution to journalArticle

292 Scopus citations

Abstract

DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The developmentally regulated demethylation of astrocyte marker genes as well as genes encoding the crucial components of the gliogenic JAK-STAT pathway is accelerated in Dnmt1-/- NPCs. Through a chromatin remodeling process, demethylation of genes in the JAK-STAT pathway leads to an enhanced activation of STATs, which in turn triggers astrocyte differentiation. Our study suggests that during the neurogenic period, DNA methylation inhibits not only astroglial marker genes but also genes that are essential for JAK-STAT signaling. Thus, demethylation of these two groups of genes and subsequent elevation of STAT activity are key mechanisms that control the timing and magnitude of astroglial differentiation.

Original languageEnglish (US)
Pages (from-to)3345-3356
Number of pages12
JournalDevelopment
Volume132
Issue number15
DOIs
StatePublished - Aug 2005

Keywords

  • Chromatin remodeling
  • CpG methylation
  • Dnmt1
  • Histone modification
  • MeCP2
  • Mouse
  • Neural differentiation
  • STAT1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Fan, G., Martinowich, K., Chin, M. H., He, F., Fouse, S. D., Hutnick, L., Hattori, D., Ge, W., Shen, Y., Wu, H., ten Hoeve, J., Shuai, K., & Sun, Y. E. (2005). DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development, 132(15), 3345-3356. https://doi.org/10.1242/dev.01912