九州大学 研究者情報
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基本情報 研究活動 教育活動 社会活動
今村 拓也(いまむら たくや) データ更新日:2019.06.25

准教授 /  医学研究院 応用幹細胞医科学部門 応用幹細胞医科学講座 基盤幹細胞学分野/統合的組織修復医学


主な研究テーマ
マウス初期胚における液性因子による転移因子制御機構
キーワード:レトロトランスポゾン 、全能性
2016.04~2018.03.
種特異的ノンコーディングRNAによるほ乳類脳神経機能の分化
キーワード:ノンコーディングRNA、エピゲノム、進化
2015.04~2018.03.
偽遺伝子挿入による種特異的非コードRNA獲得に基づく遺伝子スイッチ制御の多様化
キーワード:ノンコーディングRNA エピジェネティック  進化
2012.04~2015.03.
遺伝子配列特異的エピジェネティック制御によるマウス腹内側核の機能的性差形成
キーワード:ノンコーディングRNA エピジェネティック  性差 エストロジェン アンドロジェン
2013.04~2015.03.
マウス初期胚エピゲノム変換に資するプロモーター非コードRNA機能の解明
キーワード:ノンコーディングRNA エピジェネティック  初期胚 リプログラミング
2013.04~2015.03.
研究業績
主要著書
1. Takuya Imamura, Detection of bidirectional promoter-derived lncRNAs from small-scale samples using pre-amplification-free directional RNA-seq methods. In : Kiho Lee (ed), Zygotic Genome Activation, Humana Press, 2017.04.
2. Takuya Imamura, Manipulation of promoter- associated noncoding RNAs in mouse early embryos for controlling sequence-specific epigenetic status. In: Sara Napoli (ed), Promoter Associated RNA, Humana Press, 2017.04.
主要原著論文
1. Tsukasa Sanosaka, Takuya Imamura, Nobuhiko Hamazaki, Muh Chyi Chai, Katsuhide Igarashi, Maky Ideta-Otsuka, Fumihito Miura, Takashi Ito, Nobuyuki Fujii, Kazuho Ikeo, Kinichi Nakashima, DNA Methylome Analysis Identifies Transcription Factor-Based Epigenomic Signatures of Multilineage Competence in Neural Stem/Progenitor Cells, Cell Reports, 10.1016/j.celrep.2017.08.086, 20, 12, 2992-3003, 2017.09, [URL], Regulation of the epigenome during in vivo specification of brain stem cells is still poorly understood. Here, we report DNA methylome analyses of directly sampled cortical neural stem and progenitor cells (NS/PCs) at different development stages, as well as those of terminally differentiated cortical neurons, astrocytes, and oligodendrocytes. We found that sequential specification of cortical NS/PCs is regulated by two successive waves of demethylation at early and late development stages, which are responsible for the establishment of neuron- and glia-specific low-methylated regions (LMRs), respectively. The regulatory role of demethylation of the gliogenic genes was substantiated by the enrichment of nuclear factor I (NFI)-binding sites. We provide evidence that de novo DNA methylation of neuron-specific LMRs establishes glia-specific epigenotypes, essentially by silencing neuronal genes. Our data highlight the in vivo implications of DNA methylation dynamics in shaping epigenomic features that confer the differentiation potential of NS/PCs sequentially during development..
2. Takuya Imamura, Evolutionary acquisition of promoterassociated non-coding RNA (pancRNA) repertoires diversifies species-dependent gene activation mechanisms in mammals, BMC GENOMICS, 10.1186/s12864-017-3662-1, 18, 2017.04.
3. 今村 拓也, lncRNAの進化と種特異性, 化学同人, 328-338, 2016.07.
4. Takuya Imamura, Bidirectional promoters link cAMP signaling with irreversible differentiation through promoter-associated non-coding RNA (pancRNA) expression in PC12 cells., Nucleic Acids Research, doi:10.1093/nar/gkw113, 2016.03.
5. 今村 拓也, R+rGADEM, 秀潤社, 322-325, 2015.10.
6. 今村 拓也, Gene activation-associated long noncoding RNAs function in mouse preimplantation development, DEVELOPMENT, 10.1242/dev.116996, 142, 5, 910-920, 2015.03.
7. Takuya Imamura, Epigenetic setting and reprogramming for neural cell fate determination and differentiation, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 10.1098/rstb.2013.0511, 369, 1652, 2014.09.
8. Masahiro Uesaka, Osamu Nishimura, Yasuhiro Go, Kinichi Nakashima, Kiyokazu Agata, Takuya Imamura, Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals, BMC Genomics, doi:10.1186/1471-2164-15-35, 15, 35, 2014.01, Background
The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism in mammals have been believed to downregulate the corresponding mRNA expression level in a pre- or post-transcriptional manner by forming short or long ncRNA-mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also rapidly accumulating. To examine the directional properties of transcription at the whole-genome level, we performed directional RNA-seq analysis of mouse and chimpanzee tissue samples.

Results
We found that there is only about 1% of the genome where both the top and bottom strands are utilized for transcription, suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on transcription start sites (TSSs) of protein-coding genes revealed that a significant fraction of them contain switching-points that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription is more prevalent than previously thought. More than 90% of head-to-head type promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly enriched in the upstream regions and downstream regions, respectively, of TSSs located in head-to-head type promoters. Genes with tissue-specific promoter-associated ncRNAs (pancRNAs) show a positive correlation between the expression of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA in facultative gene activation, whereas genes with constitutive expression generally lack pancRNAs.

Conclusions
We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression..
9. 今村 拓也, Single-stranded Noncoding RNAs Mediate Local Epigenetic Alterations at Gene Promoters in Rat Cell Lines, JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.M111.275750, 286, 40, 34788-34799, 2011.10.
10. 今村 拓也, Dynamic CpG and non-CpG methylation of the Peg1/Mest gene in the mouse oocyte and preimplantation embryo, JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.M501749200, 280, 20, 20171-20175, 2005.05.
11. Takuya Imamura, Non-coding RNA directed DNA demethylation of Sphk1 CpG island, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 10.1016/j.bbrc.2004.07.159, 322, 2, 593-600, 2004.09.
12. 今村 拓也, CpG island of rat sphingosine kinase-1 gene: tissue-dependent DNA methylation status and multiple alternative first exons, GENOMICS, 76, 1-3, 117-125, 2001.08.
主要総説, 論評, 解説, 書評, 報告書等
1. Takuya Imamura, Masahiro, Epigenetic setting and reprogramming for neural cell fate determination and differentiation., In the mammalian brain, epigenetic mechanisms are clearly involved in the regulation of self-renewal of neural stem cells and the derivation of their descendants, i.e. neurons, astrocytes and oligodendrocytes, according to the developmental timing and the microenvironment, the 'niche'. Interestingly, local epigenetic changes occur, concomitantly with genome-wide level changes, at a set of gene promoter regions for either down- or upregulation of the gene. In addition, intergenic regions also sensitize the availability of epigenetic modifiers, which affects gene expression through a relatively long-range chromatinic interaction with the transcription regulatory machineries including non-coding RNA (ncRNA) such as promoter-associated ncRNA and enhancer ncRNA. We show that such an epigenetic landscape in a neural cell is statically but flexibly formed together with a variable combination of generally and locally acting nuclear molecules including master transcription factors and cell-cycle regulators. We also discuss the possibility that revealing the epigenetic regulation by the local DNA-RNA-protein assemblies would promote methodological innovations, e.g. neural cell reprogramming, engineering and transplantation, to manipulate neuronal and glial cell fates for the purpose of medical use of these cells..
学会活動
所属学会名
日本エピジェネティクス研究会
日本獣医学会
日本発生生物学会
日本繁殖生物学会
日本分子生物学会
学協会役員等への就任
2015.06~2018.06, 日本繁殖生物学会, 編集委員.
2004.04~2009.03, 日本繁殖生物学会, 若手奨励策検討委員会.
学会大会・会議・シンポジウム等における役割
2006.09.08~2006.09.08, 第99回日本繁殖生物学会シンポ「性の戦略」, オーガナイザー.
学会誌・雑誌・著書の編集への参加状況
2018.04~2020.04, BMC Genomics, 国際, 編集委員.
2015.04~2018.03, Journal of Reproduction and Development, 国際, 編集委員.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2018年度 25  25 
2017年度 20  20 
2016年度 20        20 
2015年度 10        10 
2014年度 10        10 
2013年度
受賞
日本獣医学会生理学・生化学分科会奨励賞, 日本獣医学会生理学・生化学分科会, 2011.09.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2016年度~2020年度, 新学術領域研究, 分担, 個性を創発する神経幹細胞におけるエピジェネティックメモリーとその制御.
2016年度~2017年度, 挑戦的萌芽研究, 代表, マウス初期胚における液性因子による転移因子制御機構.
2015年度~2017年度, 基盤研究(B), 代表, 種特異的ノンコーディングRNAによるほ乳類脳神経機能の分化.
2012年度~2014年度, 基盤研究(B), 代表, 偽遺伝子挿入による種特異的非コードRNA獲得に基づく遺伝子スイッチ制御の多様化.
2013年度~2014年度, 新学術領域研究, 代表, 遺伝子配列特異的エピジェネティック制御によるマウス腹内側核の機能的性差形成.
2013年度~2014年度, 挑戦的萌芽研究, 代表, マウス初期胚エピゲノム変換に資するプロモーター非コードRNA機能の解明.

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