Updated on 2024/05/26

写真a

 
ONOGUCHI, Masahiro
 
Affiliation
Faculty of Science and Engineering, Waseda Research Institute for Science and Engineering
Job title
Junior Researcher(Assistant Professor)
Degree
博士(生命科学) ( 東京大学 )

Research Experience

  • 2021.04
    -
    Now

    Waseda University   Faculty of Science and Engineering

  • 2018.04
    -
    2021.03

    National Institute of Advanced Industrial Science and Technology

  • 2016.07
    -
    2018.03

    Keio University   School of Medicine

  • 2014.04
    -
    2016.06

    スタンフォード大学医学部 博士研究員

  • 2013.04
    -
    2014.03

    The University of Tokyo   Institute of Molecular and Cellular Biosciences

  • 2012.04
    -
    2013.03

    The University of Tokyo   Institute of Molecular and Cellular Biosciences

  • 2010.04
    -
    2012.03

    日本学術振興会 特別研究員(DC2)

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Research Areas

  • Evolutionary biology / Neuroscience-general / Molecular biology / System genome science / Genome biology   RNA

Research Interests

  • RNA-Protein interaction

  • 機能性RNA

  • ゲノム進化

  • 神経発生

  • enhancer

  • lncRNA

  • transposon

  • noncoding RNA

▼display all

Awards

  • 海外留学助成金ポストドクトラルフェローシップ

    2014.03   上原記念生命科学財団  

  • 博士論文特別奨励賞

    2013.03   東京大学大学院新領域創成科学研究科 先端生命科学専攻  

  • 研究科長賞

    2013.03   東京大学大学院新領域創成科学研究科  

 

Papers

  • Transposons contribute to the acquisition of cell type-specific cis-elements in the brain

    Kotaro Sekine, Masahiro Onoguchi*, Michiaki Hamada*(*co-corresponding authors)

    Communications Biology   6 ( 1 ) 631  2023.06  [Refereed]

    Authorship:Corresponding author

     View Summary

    Abstract

    Mammalian brains have evolved in stages over a long history to acquire higher functions. Recently, several transposable element (TE) families have been shown to evolve into cis-regulatory elements of brain-specific genes. However, it is not fully understood how TEs are important for gene regulatory networks. Here, we performed a single-cell level analysis using public data of scATAC-seq to discover TE-derived cis-elements that are important for specific cell types. Our results suggest that DNA elements derived from TEs, MER130 and MamRep434, can function as transcription factor-binding sites based on their internal motifs for Neurod2 and Lhx2, respectively, especially in glutamatergic neuronal progenitors. Furthermore, MER130- and MamRep434-derived cis-elements were amplified in the ancestors of Amniota and Eutheria, respectively. These results suggest that the acquisition of cis-elements with TEs occurred in different stages during evolution and may contribute to the acquisition of different functions or morphologies in the brain.

    DOI

    Scopus

  • Binding patterns of RNA-binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements

    Masahiro Onoguchi, Chao Zeng, Ayako Matsumaru, Michiaki Hamada

    NAR Genomics and Bioinformatics   3 ( 3 ) lqab055  2021.07  [Refereed]  [International journal]

    Authorship:Lead author

     View Summary

    <title>Abstract</title>
    Recent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA-binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.

    DOI PubMed

    Scopus

    3
    Citation
    (Scopus)
  • Association analysis of repetitive elements and R-loop formation across species

    Chao Zeng, Masahiro Onoguchi, Michiaki Hamada

    Mobile DNA   12 ( 3 ) 3 - 3  2021.01  [Refereed]  [International journal]

     View Summary

    <title>Abstract</title><sec>
    <title>Background</title>
    Although recent studies have revealed the genome-wide distribution of R-loops, our understanding of R-loop formation is still limited. Genomes are known to have a large number of repetitive elements. Emerging evidence suggests that these sequences may play an important regulatory role. However, few studies have investigated the effect of repetitive elements on R-loop formation.


    </sec><sec>
    <title>Results</title>
    We found different repetitive elements related to R-loop formation in various species. By controlling length and genomic distributions, we observed that satellite, long interspersed nuclear elements (LINEs), and DNA transposons were each specifically enriched for R-loops in humans, fruit flies, and Arabidopsis thaliana, respectively. R-loops also tended to arise in regions of low-complexity or simple repeats across species. We also found that the repetitive elements associated with R-loop formation differ according to developmental stage. For instance, LINEs and long terminal repeat retrotransposons (LTRs) are more likely to contain R-loops in embryos (fruit fly) and then turn out to be low-complexity and simple repeats in post-developmental S2 cells.


    </sec><sec>
    <title>Conclusions</title>
    Our results indicate that repetitive elements may have species-specific or development-specific regulatory effects on R-loop formation. This work advances our understanding of repetitive elements and R-loop biology.


    </sec>

    DOI PubMed

    Scopus

    12
    Citation
    (Scopus)
  • The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders

    Cheen Euong Ang, Qing Ma, Orly L Wapinski, ShengHua Fan, Ryan A Flynn, Qian Yi Lee, Bradley Coe, Masahiro Onoguchi, Victor Hipolito Olmos, Brian T Do, Lynn Dukes-Rimsky, Jin Xu, Koji Tanabe, LiangJiang Wang, Ulrich Elling, Josef M Penninger, Yang Zhao, Kun Qu, Evan E Eichler, Anand Srivastava, Marius Wernig, Howard Y Chang

    eLife   8  2019.01  [Refereed]

     View Summary

    Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1. We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases.

    DOI

  • A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development

    Masahiro Onoguchi, Yusuke Hirabayashi, Haruhiko Koseki, Yukiko Gotoh

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   109 ( 42 ) 16939 - 16944  2012.10  [Refereed]

    Authorship:Lead author

     View Summary

    The proneural basic helix-loop-helix (bHLH) transcription factor neurogenin1 (Neurog1) plays a pivotal role in neuronal differentiation during mammalian development. The spatiotemporal control of the Neurog1 gene expression is mediated by several specific enhancer elements, although how these elements regulate the Neurog1 locus has remained largely unclear. Recently it has been shown that a large number of enhancer elements are transcribed, but the regulation and function of the resulting transcripts have been investigated for only several such elements. We now show that an enhancer element located 5.8-7.0 kb upstream of the mouse Neurog1 locus is transcribed. The production of this transcript, designated utNgn1, is highly correlated with that of Neurog1 mRNA during neuronal differentiation. Moreover, knockdown of utNgn1 by a corresponding short interfering RNA inhibits the production of Neurog1 mRNA in response to induction of neuronal differentiation. We also found that production of utNgn1 is suppressed by polycomb group (PcG) proteins, which inhibit the expression of Neurog1. Our results thus suggest that a noncoding RNA transcribed from an enhancer element positively regulates transcription at the Neurog1 locus.

    DOI

    Scopus

    63
    Citation
    (Scopus)
  • Formation of cytochrome C-apatite composite layer on NaOH- and heat-treated titanium

    Yu Sogo, Atsuo Ito, Masahiro Onoguchi, Xia Li, Ayako Oyane, Noboru Ichinose

    MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS   29 ( 3 ) 766 - 770  2009.04  [Refereed]

     View Summary

    A cytochrome C (cyt C) and apatite composite layer was formed on a NaOH- and heat-treated titanium substrate (Ti substrate) by immersing the Ti substrate for one day at 25 degrees C in supersaturated calcium phosphate solutions obtained by mixing infusion fluids. When the initial supersaturation level of the calcium phosphate solution was increased, the total amount of cyt C and apatite deposited on the Ti substrate increased. On the other hand, the cyt C content in the composite layer decreased with an increase in initial supersaturation level. The morphology of the composite layer markedly changed depending on the initial supersaturation level. Therefore, the initial supersaturation level affected the formation of the cyt C and apatite composite layer. It is expected that fibroblast growth factor-2 can be immobilized on NaOH- and heat-treated titanium Substrates using the same method. (C) 2008 Elsevier B.V. All rights reserved.

    DOI

    Scopus

    4
    Citation
    (Scopus)
  • Formation of a FGF-2 and calcium phosphate composite layer on a hydroxyapatite ceramic for promoting bone formation

    Yu Sogo, Atsuo Ito, Masahiro Onoguchi, Ayako Oyane, Hideo Tsurushima, Noboru Ichinose

    BIOMEDICAL MATERIALS   2 ( 3 ) S175 - S180  2007.09  [Refereed]

     View Summary

    Fibroblast growth factor-2 (FGF-2) was immobilized on a hydroxyapatite (HAP) ceramic in supersaturated calcium phosphate solution prepared using solutions corresponding to clinically approved infusion fluids. To avoid the risk of FGF-2 denaturation, FGF-2 immobilization was carried out at 25 degrees C. FGF-2 was successfully immobilized on HAP ceramic surfaces by deposition with calcium phosphate to form a FGF-2 and calcium phosphate composite layer. A maximum of 2.72 +/- 0.01 mu g cm(-2) of FGF-2 was immobilized in the composite layer formed on the HAP ceramic under the optimum condition. A FGF-2-immobilized HAP ceramic is likely to have the ability to release a sufficient amount of FGF-2 to promote bone formation. FGF-2 released from a FGF-2-immobilized HAP ceramic maintained its biological activity, since the proliferation of fibroblastic NIH3T3 was promoted. Therefore, the FGF-2-immobilized HAP ceramic is expected to be a useful material for promoting new bone formation.

    DOI

    Scopus

    36
    Citation
    (Scopus)
  • Formation of an ascorbate-apatite composite layer on titanium

    Atsuo Ito, Yu Sogo, Yuko Ebihara, Masahiro Onoguchi, Ayako Oyane, Noboru Ichinose

    BIOMEDICAL MATERIALS   2 ( 3 ) S181 - S185  2007.09  [Refereed]

     View Summary

    An ascorbate - apatite composite layer was successfully formed on NaOH- and heat-treated titanium by coprecipitating L-ascorbic acid phosphate and low-crystalline apatite in a supersaturated calcium phosphate solution at 37 degrees C for 48 h. The supersaturated calcium phosphate solutions used have chemical compositions attainable by mixing infusion fluids officially approved for clinical use. The amount of immobilized L-ascorbic acid phosphate ranged from 1.0 to 2.3 mu g mm(-2), which is most likely to be sufficient for the in vitro osteogenic differentiation of mesenchymal stem cells on titanium. Since ascorbate is important for the collagen synthesis and subsequent osteogenesis of mesenchymal stem cells, titanium coated with the ascorbate - apatite composite layer would be useful as a scaffold in bone tissue engineering and as a bone substitute.

    DOI

    Scopus

    7
    Citation
    (Scopus)

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Books and Other Publications

  • エピジェネティクス実験スタンダード

    牛島俊和, 眞貝洋一, 塩見春彦, 編, 小野口真広, 他, 著( Part: Contributor, 274-286)

    羊土社  2017

Presentations

  • LINE1 RNAと相互作用するタンパク質の網羅的解析とクロマチン制御機構の解明

    小野口真広, 足達俊吾, 浜田道昭

    第46回日本分子生物学会年会 

    Presentation date: 2023.12

  • Comprehensive analysis of the LINE1-associated proteins and estimation of novel regulators of LINE1

    Masahiro Onoguchi, Shungo Adachi, Michiaki Hamada

    Presentation date: 2023.07

    Event date:
    2023.07
     
     
  • Comprehensive analysis of the LINE1-associated proteins and estimation of novel regulators of LINE1

    Masahiro Onoguchi, Shungo Adachi, Michiaki Hamada

    Cold Spring Harhor Asia RNA Biology 

    Presentation date: 2022.12

    Event date:
    2022.12
     
     
  • LINE1配列と相互作用するタンパク質の網羅的解析と新規制御因子の探索

    小野口真広, 足達俊吾, 浜田道昭

    第45回日本分子生物学会年会 

    Presentation date: 2022.12

    Event date:
    2022.11
    -
    2022.12
  • Binding Patterns of RNA Binding Proteins To Repeat-Derived RNA Sequences Reveal Putative Functional RNA Elements

    小野口真広, 曽超, 松丸綾子, 浜田道昭

    日本R N A学会年会 

    Presentation date: 2021.07

  • Binding patterns of RNA binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements

    Masahiro Onoguchi, Chao Zeng, Ayako Matsumaru, Michiaki Hamada

    2021 Keystone Symposia Conference, Non-Coding RNAs: Biology and Applications 

    Presentation date: 2021.05

    Event date:
    2021.05
     
     
  • LINE1配列に結合するRNA結合タンパク質の同定とRNA機能エレメントの推定

    小野口真広, 浜田道昭

    第43回日本分子生物学会年会 

    Presentation date: 2020.12

    Event date:
    2020.12
     
     
  • Bioinformatic approaches for understanding RNA reincarnation

    Chao Zeng, Masahiro Onoguchi, Michiaki Hamada

    Presentation date: 2020.12

    Event date:
    2020.12
     
     
  • Analysis and estimation of functional domains of lncRNAs using eCLIP data

    Masahiro Onoguchi, Chao Zeng, Yukiteru Ono, Michiaki Hamada

    2020 Keystone Symposia Conference, Noncoding RNAs: Mechanism, Function and Therapies 

    Presentation date: 2020.01

    Event date:
    2020.01
     
     
  • eCLIPデータを用いた機能性RNA反復配列の推定

    小野口真広, 曽超, 松丸綾子, 浜田道昭

    第42回日本分子生物学会年会 

    Presentation date: 2019.12

    Event date:
    2019.12
     
     

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Research Projects

  • Overview and Systematic Understanding of Biological Phase Separation Based on RNA-Centric Molecular Networks

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2023.04
    -
    2026.03
     

  • eCLIPデータを用いた機能性RNA反復配列の探索

    日本学術振興会  科学研究費助成事業

    Project Year :

    2021.04
    -
    2024.03
     

    小野口 真広

     View Summary

    近年の報告により、遺伝子のイントロンや長鎖非翻訳RNA (long noncoding RNA; lncRNA)に含まれる反復配列がRNA結合タンパク質(RNA binding protein; RBP)の結合標的配列となることで、RNAのスプライシング制御やlncRNAの機能に重要な役割を果たすことが明らかにされつつある。これらの報告は、ゲノム中に散在する反復配列が「RNA機能ドメイン」として重要であることを示唆している。しかしながら反復配列の解析の困難さなどのため、どのような反復配列にどのような機能があるのか、その全容は十分にわかっていない。そこで本研究では、公共のデータベース(ENCODE, eCLIP)を用いてRNA反復配列に対するRBP結合配列を推定し、実験的な検証を加えることで、RNA反復配列の中から機能性RNA配列を探索することを目的とした。
    当該年度では、ENCODEのeCLIPデータベースについて独自のパイプラインを用いて解析を行い、反復配列内に存在する機能性RNA配列候補を網羅的に探索した。その結果、多数の機能性RNA配列候補を得ることに成功した。例えば、ヒトにおけるメジャーなトランスポゾンであるLINE1ファミリーの配列内に、ヘテロクロマチン形成に関与するRBP(SAFB)を含む複数のRBPが結合することが示唆された。この配列は2つのRNAヘアピン構造からなり、この配列を遺伝子内にもつ遺伝子の発現は、全ての遺伝子の発現量と比べて有意に抑制されていることが示唆された。これらの結果は遺伝子内に存在するLINE1配列の特定の断片が、内在の遺伝子発現の制御に関与している可能性を示している。
    本研究はRNA反復配列の新たな役割の解明の手がかりとなり、RNA配列中に存在する新たな「機能ドメイン」の発見に貢献することが期待される。

  • リピート要素のde novo発見に基づく長鎖ノンコーディングRNAの機能の解明

    日本学術振興会  科学研究費助成事業

    Project Year :

    2020.04
    -
    2023.03
     

    浜田 道昭, 福永 津嵩, 足達 俊吾, 小野口 真広

  • Understanding of how the cell distinguishes piRNA precursors and transcripts from cellular counterparts

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2017.04
    -
    2020.03
     

    Onoguchi Masahiro

     View Summary

    piRNA (PIWI-interacting RNA) is required for the suppression of transposons in the germline and disruption of the piRNA pathway leads to infertility. piRNAs are processed from piRNA precursors and key question is how RNAs are selected as piRNA precursors. Previous studies have shown that piRNA precursor have a determinant sequence that is necessary for and sufficient to the piRNA production. However, which proteins are associated with the determinant sequence remains elusive. Here we analyzed the proteins which associate with the piRNA determinant sequence in OSC cells. Using ChIRP-MS method, we identified 192 proteins which interact with the GFP-Flam-1st exon reporter. We found multiple novel proteins with unknown function as well as the proteins those are shown to be associated with PIWI and/or required for piRNA biogenesis. Our data will provide not only promising candidates for key proteins of piRNA precursor selection but also perspective of the whole piRNA biogenesis pathway.

  • エンハンサーによるlncRNAを介した新しい遺伝子発現制御機構の解析

    日本学術振興会  科学研究費助成事業

    Project Year :

    2013.04
    -
    2014.03
     

    小野口 真広

     View Summary

    本年度の実験計画に基づき、まず、utNgn1が標的遺伝子であるNeurog1のプロモーター領域のヒストン修飾に影響を与えるかを、クロマチン免疫沈降法(ChIP)により検討した。大脳新皮質由来の神経系前駆細胞を用いてutNgn1をノックダウンし、転写活性化状態に関連するヒストン修飾および転写抑制に関連するヒストン修飾抗体を用いてChIPを行った。その結果、Neurog1プロモーターにおいては、これらのヒストン修飾レベルに大きな変化は見られなかった。そこで次に、utNgn1がRNA ポリメラーゼIIのリクルートあるいは転写開始や転写伸長などに関与している可能性を RNAポリメラーゼII抗体を用いてChIPにより検討した。その結果興味深いことに、 utNgn1がNeurog1の転写の開始や伸長に関与している可能性を示唆する結果が得られた。さらにutNgn1のエンハンサーとしての機能を検討するために、エンハンサーとプロモーター領域の近接具合をChromosome Conformation Capture(3C)法により評価した。その結果、神経系前駆細胞がニューロン分化する過程で、Neurog1遺伝子座のエンハンサー−プロモーター間が近接する可能性が示唆された。さらにこの近接とutNgn1の関係を検討した。これらの結果から、utNgn1がどのようにNeurog1の転写促進に関与しているのかについて、非常に示唆的な結果が得られた。 本結果に基づきさらに詳細に解析を進めることで、lncRNAの新しい作用機序が明らかになることが期待される。