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Takuya Imamura Last modified date:2019.06.25

Associate Professor / Department of Stem Cell Biology and Medicine
Department of Stem Cell Biology and Medicine
Faculty of Medical Sciences

Regulation of non-coding RNA contributes to the complete cessation of cell proliferation of neuron-like cells .
Gene activation-associated long noncoding RNAs function in mouse preimplantation development .
Academic Degree
Ph. D.
Field of Specialization
Genetics and Epigenetics
Research Interests
  • Regulatory mechanisms of retrotransposition mediated by extracellular signals in mouse preimplantation embryos
    keyword : retrotransposon, topipotency
  • Species diversification of brain function by acquisition of non-coding RNA in mammals
    keyword : non-coding RNA, epigenome, evolution
  • Diversification of gene expression control by the acquisition of the retrogene-derived species-specific non-coding RNAs
    keyword : non-coding RNA, epigenetic, evolution
  • Sexual differentiation of mouse ventromedial hypothalamic nuclei by sequence-specific epigenetic control
    keyword : non-coding RNA, epigenetic, sexual differentiation, estrogen, androgen
  • Functions of the promoter-associated non-coding RNAs for the epigenetic reprogramming during mouse preimplantation development
    keyword : non-coding RNA, epigenetic, embryo, reprogramming
Academic Activities
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.
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..
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, 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. 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.
4. 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.
5. 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.
6. 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.

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.

We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression..
7. 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.
8. 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.
9. 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.
10. 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.
Membership in Academic Society
  • The Japanese Society for Epigenetics
  • The Japanese Society of Veterinary Science
  • Japan Society of Developmental Biologists
  • Society for Reproduction and Development
  • Molecular Biology Society of Japan
Educational Activities
I am involved in the leading and educational activities in which bridging stem cell biology and epigenetics is emphasized as a basis for neural networking.