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Gene Regulation and Epigenetics

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Mechanisms of transcription-dependent gene clustering in differentiating embryonic neural stem cells

  • P3-033
  • 伊藤 謙治 / Kenji Ito:1 佐野坂 司 / Sanosaka Tsukasa:2 五十嵐 勝秀 / Igarashi Katsuhide:3 大塚 まき / Otsuka I Maky:3 魚崎 祐一 / uosaki Yuichi :1 野口 東美 / noguchi Azumi:1 荒川 浩一 / Arakawa Hirokazu:1 中島 欽一 / Nakashima Kinichi:2 滝沢 琢己 / Takizawa Takumi:1 
  • 1:群馬大院医・小児科学 / Dept Pediatrics, Univ of Gunma, Gunma, Japan 2:九州大院医・基盤幹細胞 / Dept Stemcellbiol, Univ of Kyusyu, Fukuoka, Japan 3:星薬大・先端生命科学 / L-StaR, Hoshi University School of Pharmacy and Pharmaceutical Science, Tokyo, Japan 

Differentiation of neural stem cells (NSCs) in the central nervous system (CNS) is temporally and spatially regulated at least in part through epigenetic modifications of chromatin. Although evidence shows that subnuclear spatial positioning of genes plays a role in the transcriptional regulation, little is known about its relevance in gene expression and differentiation in the CNS. The purpose of this study is to explore mechanisms underlying differentiation of NSCs by analyzing changes in spatial gene positioning, for instance, gene clustering of specific genes. NSCs were prepared from murine telencephalons at embryonic day 14 and stimulated with leukemia inhibitory factor (LIF) to induce astrocyte differentiation. With an enhanced circular chromosome conformation capture (e4C) assay, we found ~1,000 genes clustering with a gene locus of an astrocyte marker, glial fibrillary acidic protein (Gfap). Among them, 13 genes were expressed and clustered with Gfap specifically in LIF-induced astrocytes. We further explored detailed mechanisms of gene clustering focusing on one of the 13 putative genes, oncostatin M receptor (Osmr). Chromatin immnoprecipitation (ChIP) assay showed that STAT3 was bound to its recognition sequences on Gfap and Osmr, and the binding was temporally correlated with their transcription activity. We found that Brahma-related gene 1 (BRG1), the catalytic subunit of mammalian SWI/SNF chromatin remodeling enzymes, was recruited to Gfap and Osmr, in prior to the gene clustering. We are currently investigating whether BRG1 is involved in regulation of gene clustering.

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