Iwasaki, Yuka

写真a

Affiliation

School of Medicine, Department of Molecular Biology (Shinanomachi)

Position

Associate Professor

E-mail Address

E-mail address

Related Websites

Career 【 Display / hide

  • 2020.05
    -
    Present

    Keio University, School of Medicine, Associate Professor

  • 2016.08
    -
    2020.04

    Keio University, School of Medicine, Assistant Professor

  • 2012.08
    -
    2016.07

    Keio Universiy, School of Medicine, Instructor

  • 2011.04
    -
    2012.07

    Keio University, School of Medicine, Postdoctoral researcher

Academic Background 【 Display / hide

  • 2011.03

    Keio University, Graduate School of Media and Governance

    Graduate School, Completed

  • 2006.03

    Keio University, Faculty of Environment and Information Studies

    University, Graduated

Academic Degrees 【 Display / hide

  • Ph.D., Keio University, Coursework, 2011.03

 

Research Areas 【 Display / hide

  • Genome biology

  • System genome science

  • Molecular biology

Research Keywords 【 Display / hide

  • RNA silencing

  • Epigenome

  • Epigenetics

  • Chromatin

  • Genome

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Papers 【 Display / hide

  • Nuclear RNA export factor variant initiates piRNA‐guided co‐transcriptional silencing

    Murano K, Iwasaki YW, Ishizu H, Mashiko A, Shibuya A, Kondo S, Adachi S, Suzuki S, Saito K, Natsume T, Siomi MC, Siomi H

    the EMBO journal e102870   e102870 2019.08

    Joint Work, Accepted,  ISSN  1460-2075

     View Summary

    The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15. Panx-Nxf2-P15 complex formation is necessary in the silencing by stabilizing protein levels of Nxf2 and Panx. Notably, ectopic targeting of Nxf2 initiates co-transcriptional repression of the target reporter in a manner independent of H3K9me3 marks or H1. However, continuous silencing requires HP1a and H1. In addition, Nxf2 directly interacts with target TE transcripts in a Piwi-dependent manner. These findings suggest a model in which the Panx-Nxf2-P15 complex enforces the association of Piwi with target transcripts to trigger co-transcriptional repression, prior to heterochromatin formation in the nuclear piRNA pathway. Our results provide an unexpected connection between an NXF variant and small RNA-mediated co-transcriptional silencing.

  • Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification

    Sadahiro, T., Isomi, M., Muraoka, N., Kojima, H., Haginiwa, S., Kurotsu, S., Tamura, F., Tani, H., Tohyama, S., Fujita, J., Miyoshi, H., Kawamura, Y., Goshima, N., Iwasaki, Y. W., Murano, K., Saito, K., Oda, M., Andersen, P., Kwon, C., Uosaki, H., Nishizono, H., Fukuda, K. and Ieda, M.

    Cell Stem Cell 23 ( 3 ) 382 - 395 e5 2018.09

    ISSN  1875-9777

     View Summary

    The mesoderm arises from pluripotent epiblasts and differentiates into multiple lineages; however, the underlying molecular mechanisms are unclear. Tbx6 is enriched in the paraxial mesoderm and is implicated in somite formation, but its function in other mesoderms remains elusive. Here, using direct reprogramming-based screening, single-cell RNA-seq in mouse embryos, and directed cardiac differentiation in pluripotent stem cells (PSCs), we demonstrated that Tbx6 induces nascent mesoderm from PSCs and determines cardiovascular and somite lineage specification via its temporal expression. Tbx6 knockout in mouse PSCs using CRISPR/Cas9 technology inhibited mesoderm and cardiovascular differentiation, whereas transient Tbx6 expression induced mesoderm and cardiovascular specification from mouse and human PSCs via direct upregulation of Mesp1, repression of Sox2, and activation of BMP/Nodal/Wnt signaling. Notably, prolonged Tbx6 expression suppressed cardiac differentiation and induced somite lineages, including skeletal muscle and chondrocytes. Thus, Tbx6 is critical for mesoderm induction and subsequent lineage diversification.

  • Hierarchical roles of mitochondrial Papi and Zucchini in Bombyx germline piRNA biogenesis

    Nishida, K. M., Sakakibara, K., Iwasaki, Y. W., Yamada, H., Murakami, R., Murota, Y., Kawamura, T., Kodama, T., Siomi, H. and Siomi, M. C.

    Nature 555 ( 7695 ) 260 - 264 2018.03

    ISSN  1476-4687

     View Summary

    PIWI-interacting RNAs (piRNAs) are small regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity in animal germ lines. piRNA 3' end formation in the silkworm Bombyx mori has been shown to be mediated by the 3'-to-5' exonuclease Trimmer (Trim; known as PNLDC1 in mammals), and piRNA intermediates are bound with PIWI anchored onto mitochondrial Tudor domain protein Papi. However, it remains unclear whether the Zucchini (Zuc) endonuclease and Nibbler (Nbr) 3'-to-5' exonuclease, both of which have pivotal roles in piRNA biogenesis in Drosophila, are required for piRNA processing in other species. Here we show that the loss of Zuc in Bombyx had no effect on the levels of Trim and Nbr, but resulted in the aberrant accumulation of piRNA intermediates within the Papi complex, and that these were processed to form mature piRNAs by recombinant Zuc. Papi exerted its RNA-binding activity only when bound with PIWI and phosphorylated, suggesting that complex assembly involves a hierarchical process. Both the 5' and 3' ends of piRNA intermediates within the Papi complex showed hallmarks of PIWI 'slicer' activity, yet no phasing pattern was observed in mature piRNAs. The loss of Zuc did not affect the 5'- and 3'-end formation of the intermediates, strongly supporting the idea that the 5' end of Bombyx piRNA is formed by PIWI slicer activity, but independently of Zuc, whereas the 3' end is formed by the Zuc endonuclease. The Bombyx piRNA biogenesis machinery is simpler than that of Drosophila, because Bombyx has no transcriptional silencing machinery that relies on phased piRNAs.

  • Profiling Open Chromatin Structure in the Ovarian Somatic Cells Using ATAC-seq

    Murano, K., Iwasaki, Y. W. and Siomi, H.

    Methods Mol Biol 1680   165 - 177 2018

    ISSN  1940-6029

     View Summary

    The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was recently established as a method to profile open chromatin, which overcomes the sample size limitations of the alternative methods DNase/MNase-seq. To investigate the role of Piwi in heterochromatin formation around transposable element loci, we have used ATAC-seq to examine chromatin accessibility at target transposable elements in a Drosophila cultured cell line, ovarian somatic cells (OSCs). In this chapter, we describe our method to profile open chromatin structure in OSCs using ATAC-seq.

  • Deep sequencing and high-throughput analysis of PIWI-associated small RNAs

    Iwasaki, Y. W., Ishino, K. and Siomi, H.

    Methods 126   66 - 75 2017.08

    ISSN  1095-9130

     View Summary

    Small RNAs are now known to be major regulatory factors of gene expression. Emerging methods based on deep-sequencing have enabled the analysis of small RNA expression in a high-throughput manner, leading to the identification of large numbers of small RNAs in various species. Moreover, profiling small RNA data together with transcriptome data enables transcriptional and post-transcriptional regulation mediated by small RNAs to be hypothesized. Here, we isolated PIWIL1 (MIWI)-associated small RNAs from mouse testes, and performed small RNA-seq analysis. In addition, directional RNA-seq was performed using Piwil1 mutant mouse testes. Using these data, we describe protocols for analyzing small RNA-seq reads to obtain profiles of small RNAs associated with PIWI proteins. We also present bioinformatic protocols for analyzing RNA-seq reads that aim to annotate expression of piRNA clusters and identify genes regulated by piRNAs.

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Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • Regulation of chromatin state and gene expression by small RNAs

    2019.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Yuka Iwasaki, Grant-in-Aid for Scientific Research on Innovative Areas, Research grant, Principal Investigator

  • Germline genome integrity maintained by small RNA-mediated chromatin regulation

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Yuka Iwasaki, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • Chromatin regulation by small non-coding RNAs

    2017.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Yuka Iwasaki, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • Recognition of self and non-self in the genome by small RNAs and chromatin factors

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Yuka Iwasaki, Grant-in-Aid for Young Scientists (A), Principal Investigator

  • Epigenetic regulation by small non-coding RNAs

    2015.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Yuka Iwasaki, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

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Courses Taught 【 Display / hide

  • MOLECULAR BIOLOGY 2

    2020

  • MOLECULAR BIOLOGY 1

    2020

  • GENOME SCIENCES

    2020

  • MOLECULAR BIOLOGY 2

    2019