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Gene Regulation and Epigenetics

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Identification of plastic genes by transcriptome and ChIP-seq of Otx2 homeoprotein

  • P3-036
  • 酒井 晶子 / Akiko Sakai:1 中戸 隆一郎 / Ryuichiro Nakato:2 原 範和 / Norikazu Hara:3 柳川 右千夫 / Yuchio Yanagawa:4 桑野 良三 / Ryozo Kuwano:3 白髭 克彦 / Katsuhiko Shirahige:2 杉山 清佳 / Sayaka Sugiyama:1 
  • 1:新潟大院・医歯・神経発達 / Grad Sch Med Dent Sci, Niigata Univ, Niigata, Japan 2:東大・分生研 / Inst Mol Cell Biosci, Univ of Tokyo, Tokyo, Japan 3:新潟大・脳研 / Brain Res Inst, Niigata Univ, Niigata, Japan 4:群馬大院・医 / Grad Sch Med, Gunma Univ, Gunma, Japan 

Juvenile brain experiences a unique time window or 'critical period' when neuronal circuits are intensively remodeled based on experience. For example, binocular vision is established in the primary visual cortex (V1) through an activity-dependent competition between the two eyes. Otx2 homeoprotein is the only known transcription factor essential for activation of the critical period in V1 (Sugiyama et al., Cell 134:508, 2008). Recently, we have reported the binding sites of Otx2 throughout the neuronal genome revealed by ChIP-seq analysis of mouse cortex (Sakai et al., Neuro2013). Among 2034 genes bearing Otx2 binding sites, factors involved in neural development, transcriptional regulations and signal transmission were enriched. Moreover, identification of critical factors for development of Parvalbumin (PV)-positive interneuron, like TrkB receptor, was consistent with the notion that Otx2 promotes their maturation to activate the plasticity. However, it is still unclear which genes are actually downstream of Otx2, and hence implicated in the plasticity. To narrow down candidate, Otx2-dependent expression was detected by transcriptome analysis. Interneurons tagged by Venus under control of VGAT promoter were sorted by flow cytometry from wild-type and Otx2-deficient cortexes. Otx2-infused cortexes also served as a transcriptome sample of gain-of-function, which would be complementary to Otx2 deficiency. Combination of ChIP-seq and transcriptome analyses would uncover important new factors implicated in the critical period regulation.

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