2021/10/25 更新

写真a

サカイ アキコ
酒井 晶子
SAKAI Akiko
所属
脳研究所 生命科学リソース研究センター 特任助教
職名
特任助教
外部リンク

学位

  • 博士(理学) ( 2003年11月   京都大学 )

  • 修士(理学) ( 1999年3月   東京工業大学 )

研究キーワード

  • genome-wide analysis

  • 加齢関連疾患

  • 臨界期

  • クロマチン

  • 染色体

  • 次世代シーケンサー

  • エピジェネティクス

  • 神経発達

  • 細胞質DNA

  • ミトコンドリア

研究分野

  • ライフサイエンス / 分子生物学  / エピジェネティクス

  • ライフサイエンス / ゲノム生物学

  • ライフサイエンス / 遺伝学

  • ライフサイエンス / 神経科学一般

経歴(researchmap)

  • 新潟大学   脳研究所 脳病態解析分野   特任助教

    2021年4月 - 現在

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  • 新潟大学   大学院医歯学総合研究科   日本学術振興会特別研究員RPD

    2018年4月 - 2021年3月

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  • 新潟大学   大学院医歯学総合研究科   科学技術振興研究員

    2016年4月 - 2018年3月

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  • 新潟大学 大学院医歯学総合研究科   Graduate School of Medical and Dental Sciences   日本学術振興会特別研究員RPD

    2013年1月 - 2016年3月

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  • 新潟大学 大学院医歯学総合研究科   Graduate School of Medical and Dental Sciences   特任助教

    2011年3月 - 2012年12月

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  • 東京工業大学 大学院生命理工学研究科   Graduate School of Bioscience and Biotechnology   特任助教

    2009年4月 - 2011年3月

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  • 東京工業大学 大学院生命理工学研究科   Graduate School of Bioscience and Biotechnology   GCOE研究員

    2008年8月 - 2009年3月

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  • ハーバード大学医学部   Dept. of Biological Chemistry and Molecular Pharmacology   ポストドクトラルフェロー / 日本学術振興会海外特別研究員

    2004年5月 - 2008年7月

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  • 京都大学 大学院生命理工学研究科   博士研究員

    2003年12月 - 2004年4月

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▶ 全件表示

経歴

  • 新潟大学   脳研究所 生命科学リソース研究センター   特任助教

    2021年4月 - 現在

学歴

  • 京都大学   理学研究科   生物科学専攻

    - 2003年

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    国名: 日本国

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  • 東京工業大学   生命理工学研究科   バイオサイエンス専攻

    - 1999年

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    国名: 日本国

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  • 国際基督教大学   教養学部   理学科 生物学専攻

    - 1997年

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    国名: 日本国

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  • 神奈川県立多摩高校

    - 1993年

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所属学協会

 

論文

  • Experience-dependent transcriptional regulation in juvenile brain development. 査読

    Sakai A, Sugiyama S

    Development, growth & differentiation   60 ( 8 )   473 - 482   2018年10月

  • Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex 査読

    Xubin Hou, Nozomu Yoshioka, Hiroaki Tsukano, Akiko Sakai, Shinji Miyata, Yumi Watanabe, Yuchio Yanagawa, Kenji Sakimura, Kosei Takeuchi, Hiroshi Kitagawa, Takao K. Hensch, Katsuei Shibuki, Michihiro Igarashi, Sayaka Sugiyama

    SCIENTIFIC REPORTS   7 ( 1 )   12646   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.

    DOI: 10.1038/s41598-017-04007-x

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  • Genome-Wide Target Analyses of Otx2 Homeoprotein in Postnatal Cortex 査読

    Akiko Sakai, Ryuichiro Nakato, Yiwei Ling, Xubin Hou, Norikazu Hara, Tomoya Iijima, Yuchio Yanagawa, Ryozo Kuwano, Shujiro Okuda, Katsuhiko Shirahige, Sayaka Sugiyama

    FRONTIERS IN NEUROSCIENCE   11   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FRONTIERS MEDIA SA  

    Juvenile brain has a unique time window, or critical period, in which neuronal circuits are remodeled by experience. Mounting evidence indicates the importance of neuronal circuit rewiring in various neurodevelopmental disorders of human cognition. We previously showed that Otx2 homeoprotein, essential for brain formation, is recaptured during postnatal maturation of parvalbumin positive interneurons (PV cells) to activate the critical period in mouse visual cortex. Cortical Otx2 is the only interneuron-enriched transcription factor known to regulate the critical period, but its downstream targets remain unknown. Here, we used ChIP-seq (chromatin immunoprecipitation sequencing) to identify genome-wide binding sites of Otx2 in juvenile mouse cortex, and interneuron-specific RNA-seq to explore the Otx2-dependent transcriptome. Otx2-bound genes were associated with human diseases such as schizophrenia as well as critical periods. Of these genes, expression of neuronal factors involved in transcription, signal transduction and mitochondria' function was moderately and broadly affected in Otx2-deficient interneurons. In contrast to reported binding sites in the embryo, genes encoding potassium ion transporters such as K(v)3.1 had juvenile cortex-specific binding sites, suggesting that Otx2 is involved in regulating fast-spiking properties during PV cell maturation. Moreover, transcripts of oxidative resistance-1 (Oxr1), whose promoter has Otx2 binding sites, were markedly downregulated in Otx2 deficient interneurons. Therefore, an important role of Otx2 may be to protect the cells from the increased oxidative stress in fast-spiking PV cells. Our results suggest that coordinated expression of Otx2 targets promotes PV cell maturation and maintains its function in neuronal plasticity and disease.

    DOI: 10.3389/fnins.2017.00307

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  • Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE 査読

    Sushmita Roy, Jason Ernst, Peter V. Kharchenko, Pouya Kheradpour, Nicolas Negre, Matthew L. Eaton, Jane M. Landolin, Christopher A. Bristow, Lijia Ma, Michael F. Lin, Stefan Washietl, Bradley I. Arshinoff, Ferhat Ay, Patrick E. Meyer, Nicolas Robine, Nicole L. Washington, Luisa Di Stefano, Eugene Berezikov, Christopher D. Brown, Rogerio Candeias, Joseph W. Carlson, Adrian Carr, Irwin Jungreis, Daniel Marbach, Rachel Sealfon, Michael Y. Tolstorukov, Sebastian Will, Artyom A. Alekseyenko, Carlo Artieri, Benjamin W. Booth, Angela N. Brooks, Qi Dai, Carrie A. Davis, Michael O. Duff, Xin Feng, Andrey A. Gorchakov, Tingting Gu, Jorja G. Henikoff, Philipp Kapranov, Renhua Li, Heather K. MacAlpine, John Malone, Aki Minoda, Jared Nordman, Katsutomo Okamura, Marc Perry, Sara K. Powell, Nicole C. Riddle, Akiko Sakai, Anastasia Samsonova, Jeremy E. Sandler, Yuri B. Schwartz, Noa Sher, Rebecca Spokony, David Sturgill, Marijke van Baren, Kenneth H. Wan, Li Yang, Charles Yu, Elise Feingold, Peter Good, Mark Guyer, Rebecca Lowdon, Kami Ahmad, Justen Andrews, Bonnie Berger, Steven E. Brenner, Michael R. Brent, Lucy Cherbas, Sarah C. R. Elgin, Thomas R. Gingeras, Robert Grossman, Roger A. Hoskins, Thomas C. Kaufman, William Kent, Mitzi I. Kuroda, Terry Orr-Weaver, Norbert Perrimon, Vincenzo Pirrotta, James W. Posakony, Bing Ren, Steven Russell, Peter Cherbas, Brenton R. Graveley, Suzanna Lewis, Gos Micklem, Brian Oliver, Peter J. Park, Susan E. Celniker, Steven Henikoff, Gary H. Karpen, Eric C. Lai, David M. MacAlpine, Lincoln D. Stein, Kevin P. White, Manolis Kellis

    SCIENCE   330 ( 6012 )   1787 - 1797   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC ADVANCEMENT SCIENCE  

    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage-and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

    DOI: 10.1126/science.1198374

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  • Transcriptional and Developmental Functions of the H3.3 Histone Variant in Drosophila 査読

    Akiko Sakai, Brian E. Schwartz, Sara Goldstein, Kami Ahmad

    CURRENT BIOLOGY   19 ( 21 )   1816 - 1820   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Changes in chromatin composition accompany cellular differentiation in eukaryotes. Although bulk chromatin is duplicated during DNA replication, replication-independent (RI) nucleosome replacement occurs in transcriptionally active chromatin and during specific developmental transitions where the genome is repackaged[1, 2]. In most animals, replacement uses the conserved H3.3 histone variant [3], but the functions of this variant have not been defined. Using mutations for the two H3.3 genes in Drosophila, we identify widespread transcriptional defects in H3.3-deficient animals. We show that mutant animals compensate for the lack of H3.3 in two ways: they upregulate the expression of the major histone H3 genes, and they maintain chromatin structure by using H3 protein for RI nucleosome replacement at active genes. Rescue experiments show that increased expression of H3 is sufficient to relieve transcriptional defects. In contrast, H3.3 is essential for male fertility, and germline cells specifically require the histone variant. Defects without H3.3 first occur around meiosis, resulting in a failure to condense, segregate, and reorganize chromatin. Rescue experiments with mutated transgenes demonstrate that H3.3-specific residues involved in RI nucleosome assembly-but not major histone modification sites-are required for male fertility. Our results imply that the H3.3 variant plays an essential role in chromatin transitions in the male germline.

    DOI: 10.1016/j.cub.2009.09.021

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  • The XNP remodeler targets dynamic chromatin in Drosophila 査読

    Jonathan I. Schneiderman, Akiko Sakai, Sara Goldstein, Kami Ahmad

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   106 ( 34 )   14472 - 14477   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL ACAD SCIENCES  

    Heterochromatic gene silencing results from the establishment of a repressive chromatin structure over reporter genes. Gene silencing is often variegated, implying that chromatin may stochastically switch from repressive to permissive structures as cells divide. To identify remodeling enzymes involved in reorganizing heterochromatin, we tested 11 SNF2-type chromatin remodelers in Drosophila for effects on gene silencing. Overexpression of five remodelers affects gene silencing, and the most potent de-repressor is the alpha-thalassaemia mental retardation syndrome X-linked (ATRX) homolog X-linked nuclear protein (XNP). Although the mammalian ATRX protein localizes to heterochromatin, Drosophila XNP is not a general component of heterochromatin. Instead, XNP localizes to active genes and to a major focus near the heterochromatin of the X chromosome. The XNP focus corresponds to an unusual decondensed satellite DNA block, and both active genes and the XNP focus are sites of ongoing nucleosome replacement. We suggest that the XNP remodeler modulates nucleosome dynamics at its target sites to limit chromatin accessibility. Although XNP at active genes may contribute to gene silencing, we find that a single focus is present across Drosophila species and that perturbation of this site cripples heterochromatic gene silencing. Thus, the XNP focus appears to be a functional genetic element that can contribute to gene silencing throughout the nucleus.

    DOI: 10.1073/pnas.0905816106

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  • Genome-wide profiling of salt fractions maps physical properties of chromatin 査読

    Steven Henikoff, Jorja G. Henikoff, Akiko Sakai, Gabriel B. Loeb, Kami Ahmad

    GENOME RESEARCH   19 ( 3 )   460 - 469   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT  

    We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mono-nucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and unbound intermediates in active processes, thus providing a simple, powerful strategy for mapping epigenome dynamics.

    DOI: 10.1101/gr.087619.108

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  • Condensin but not cohesin SMC heterodimer induces DNA reannealing through protein-protein assembly 査読

    A Sakai, K Hizume, T Sutani, K Takeyasu, M Yanagida

    EMBO JOURNAL   22 ( 11 )   2764 - 2775   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Condensin and cohesin are chromosomal protein complexes required for chromosome condensation and sister chromatid cohesion, respectively. They commonly contain the SMC ((s) under bar tructural (m) under bar aintenance of (c) under bar hromosomes) subunits consisting of a long coiled-coil with the terminal globular domains and the central hinge. Condensin and cohesin holo-complexes contain three and two non-SMC subunits, respectively. In this study, DNA interaction with cohesin and condensin complexes purified from fission yeast was investigated. The DNA reannealing activity is strong for condensin SMC heterodimer but weak for holo-condensin, whereas no annealing activity is found for cohesin heterodimer SMC and Rad21-bound heterotrimer complexes. One set of globular domains of the same condensin SMC is essential for the DNA reannealing activity. In addition, the coiled-coil and hinge region of another SMC are needed. Atomic force microscopy discloses the molecular events of DNA reannealing. SMC assembly that occurs on reannealing DNA seems to be a necessary intermediary step. SMC is eliminated from the completed double-stranded DNA. The ability of heterodimeric SMC to reanneal DNA may be regulated in vivo possibly through the non-SMC heterotrimeric complex.

    DOI: 10.1093/emboj/cdg247

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  • Condensin architecture and interaction with DNA: Regulatory non-SMC subunits bind to the head of SMC heterodimer 査読

    SH Yoshimura, K Hizume, A Murakami, T Sutani, K Takeyasu, M Yanagida

    CURRENT BIOLOGY   12 ( 6 )   508 - 513   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CELL PRESS  

    Condensin and cohesin are two protein complexes that act as the central mediators of chromosome condensation and sister chromatid cohesion, respectively. The basic underlying mechanism of action of these complexes remained enigmatic. Direct visualization of condensin and cohesin was expected to provide hints to their mechanisms. They are composed of heterodimers of distinct structural maintenance of chromosome (SMC) proteins and other non-SMC subunits. Here, we report the first observation of the architecture of condensin and its interaction with DNA by atomic force microscopy (AFM). The purified condensin SMC heterodimer shows a head-tail structure with a single head composed of globular domains and a tail with the coiled-coil region. Unexpectedly, the condensin non-SMC trimers associate with the head of SMC heterodimers, producing a larger head with the tail. The heteropentamer is bound to DNA in a distributive fashion, whereas condensin SMC heterodimers interact with DNA as aggregates within a large DNA-protein assembly. Thus, non-SMC trimers may regulate the ATPase activity of condensin by directly interacting with the globular domains of SMC heterodimer and alter the mode of DNA interaction. A model for the action of heteropentamer is presented.

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  • Characterization of fission yeast cohesin: essential anaphase proteolysis of Rad21 phosphorylated in the S phase 査読

    T Tomonaga, K Nagao, Y Kawasaki, K Furuya, A Murakami, J Morishita, T Yuasa, T Sutani, SE Kearsey, F Uhlmann, K Nasmyth, M Yanagida

    GENES & DEVELOPMENT   14 ( 21 )   2757 - 2770   2000年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COLD SPRING HARBOR LAB PRESS  

    Cohesin complex acts in the formation and maintenance of sister chromatid cohesion during and after S phase. Budding yeast Scc1p/Mcd1p, an essential subunit, is cleaved and dissociates from chromosomes in anaphase, leading to sister chromatid separation. Most cohesin in higher eukaryotes, in contrast, is dissociated from chromosomes well before anaphase. The universal role of cohesin during anaphase thus remains to be determined. We report here initial characterization of four putative cohesin subunits, Psm1, Psm3, Rad21, and Psc3, in fission yeast. They are essential for sister chromatid cohesion. Immunoprecipitation demonstrates stable complex formation of Rad21 with Psm1 and Psm3 but not with Psc3. Chromatin immunoprecipitation shows that cohesin subunits are enriched in broad centromere regions and that the level of centromere-associated Rad21 did not change from metaphase to anaphase, very different from budding yeast. In contrast, Rad21 containing similar cleavage sites to those of Scc1p/Mcd1p is cleaved specifically in anaphase. This cleavage is essential, although the amount of cleaved product is very small(<5%). Mis4, another sister chromatid cohesion protein, plays an essential role for loading Rad21 on chromatin. A simple model is presented to explain the specific behavior of fission yeast cohesin and why only a tiny fraction of Rad21 is sufficient to be cleaved for normal anaphase.

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MISC

受賞

  • ショートトーク賞(奨励賞)

    2008年5月   日本エピジェネティクス研究会   H3.3ヒストンバリアントは転写およびクロマチン領域の制御に必要である

    酒井 晶子

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共同研究・競争的資金等の研究

  • 幼年期の脳発達を司る神経細胞種特異的な遺伝子発現調節:コヒーシンの役割

    研究課題/領域番号:21K06389  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    酒井 晶子

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    担当区分:研究代表者 

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 経験による神経回路の発達機構をクロマチン動態から解明する

    2019年10月

    武田科学振興財団  医学系研究助成 

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  • 臨界期可塑性におけるコヒーシンを介したクロマチン構造制御のメカニズム

    2018年4月 - 2021年3月

    科学研究費補助金 基盤研究(C) 

    酒井 晶子

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    担当区分:研究代表者  資金種別:競争的資金

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  • 経験依存的な神経回路可塑性をもたらすクロマチン構造変化の解析

    2018年4月 - 2021年3月

    日本学術振興会  特別研究員奨励費 

    酒井 晶子

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    担当区分:研究代表者  資金種別:競争的資金

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  • 発達期の脳の細胞種特異的クロマチン動態から解明する神経回路可塑性のメカニズム

    2016年4月 - 2018年3月

    科学研究費補助金 挑戦的萌芽研究 

    酒井 晶子

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    担当区分:研究代表者  資金種別:競争的資金

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  • 神経回路の可塑性を制御するクロマチン動態の解析

    2013年1月 - 2016年3月

    日本学術振興会  特別研究員奨励費 

    酒井晶子

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    担当区分:研究代表者  資金種別:競争的資金

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  • 細胞老化に伴うヘテロクロマチン領域形成のゲノム学的手法による機能解析

    2011年4月 - 2013年3月

    科学研究費補助金 若手研究(B) 

    酒井晶子

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    担当区分:研究代表者  資金種別:競争的資金

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担当経験のある授業科目(researchmap)

  • 機能生理学

    2019年1月
    -
    現在
    機関名:新潟大学

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  • 医学研究実習

    機関名:新潟大学

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担当経験のある授業科目

  • 機能生理学

    2021年
    -
    現在
    機関名:新潟大学

  • 機能生理学

    2021年
    -
    現在
    機関名:新潟大学

 

社会貢献活動

  • 中高生サイエンス・セミナー

    役割:講師

    新潟大学男女共同参画推進室  2019年1月 - 2021年3月

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