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Chromatin (Epigenetic) regulation of neuronal development

開催日 2014/9/12
時間 9:00 - 11:00
会場 Room A(Main Hall)
Chairperson(s) 後藤 由季子 / Yukiko Gotoh (東京大学大学院薬学系研究科 / Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan)
内匠 透 / Toru Takumi (理化学研究所 脳科学総合研究センター / RIKEN Brain Science Institute, Japan)

DNA demethylation-mediated acquisition of astrocyte differentiation potential by neural stem cells during brain development

  • S2-A-1-2
  • 中島 欽一 / Kinichi Nakashima:1 
  • 1:九州大学大学院医学研究院 / Dep Stem Cell Biol Med, Grad Sch Med Sci, Kyushu Univ, Japan 

During mid-gestation, mammalian neural stem cells (NSCs) are restricted to differentiate only into neurons. Meanwhile, the generation of astrocytes is prevented, owing to the heavily methylated status of astrocyte-specific gene promoters. The mechanism on how subsequent switch releases astrocytic genes from suppression remains unknown. We have previously shown that activation of Notch signaling in NSCs, as facilitated by committed neuronal precursors and immature neurons expressing Notch ligands, granted their neighboring NSCs with the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NSCs induces expression of the transcription factor nuclear factor I (NFI), which binds to a typical astrocytic gene, glial fibrillary acidic protein (gfap) promoter, resulting in demethylation of the gene. However, it has not been extensively examined whether this process of demethylation can be applied commonly to many other astrocytic genes. Thus, by using the post-bisulfite adaptor tagging (PBAT) method, we have conducted whole-genome bisulfite sequencing of NSC purified from mouse forebrain at distinct developmental stages. In line with our hypothesis and previous findings, as gestation proceeds, many astrocytic genes are indeed demethylated, and notably, NFI-binding sequences are located at close proximity to these demethylated regions. These findings suggest that NFI-mediated demethylation plays a crucial role in the acquisition of astrocyte differentiation potential among NSCs during brain development.

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