Quantification of physical parameters and construction of theoretical models to understand Chromatin Potential

• Project Area: Chromatin potential for gene regulation
• Project/Area Number: 18H05529
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institute of Genetics
• Principal Investigator: 木村 暁 国立遺伝学研究所, 遺伝メカニズム研究系, 教授 (10365447)
• Co-Investigator(Kenkyū-buntansha): 坂上 貴洋 青山学院大学, 理工学部, 教授 (30512959)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥117,650,000 (Direct Cost: ¥90,500,000、Indirect Cost: ¥27,150,000); Fiscal Year 2022: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000); Fiscal Year 2021: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000); Fiscal Year 2020: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000); Fiscal Year 2019: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000); Fiscal Year 2018: ¥33,410,000 (Direct Cost: ¥25,700,000、Indirect Cost: ¥7,710,000)
• Keywords: 細胞核 / クロマチン / 粘弾性 / 転写制御 / クロマチン構造 / ポリマー物理学 / 線虫 / 発生

Outline of Annual Research Achievements

本研究では、クロマチン構造を変化させ遺伝子発現を制御するものとして、細胞核のサイズやクロマチンの動きやすさ等の物理的要因に着目して、そのメカニズムと役割を理解することを目的としている。そのために、次の３つの解析を進めている。
(A) クロマチン濃度とその遺伝子制御能の計測
(B) クロマチン運動とその遺伝子制御能の計測
(C) 理論モデルの構築
２０２１年度は、(A)に関連して研究代表者らが線虫胚発生で計測したクロマチンの濃度と運動の関係を、(C)に関連して研究分担者が構築した理論で説明することに成功した実績の論文投稿を行った。査読の過程で多くのコメントを査読者からもらい、それに対応する様々な解析を行った。その結果、より普遍的な理論へと成果を進化させることができた。本論文は年度末にPhysical Review Letters誌に受理され、2022年度に発行される。高分子の濃度と運動性を直接的に結びつける理論的枠組みはこれまでになく、クロマチンに限らず、高分子ダイナミクスの理論として重要な成果である。また研究代表者と分担者は関連する実験と理論を解説する総説を共著で執筆し、これも受理され2022年度に発行予定となっている。また(A)と(B)に関連して、研究代表者は転写活性化部位を可視化する、活性型RNAポリメラーゼIIのプローブを線虫胚で発現させる実験系の確立を行い、測定を進めている。さらに(C)に関連して、研究分担者はクロマチン運動を記述する高分子理論モデルの開発を進めた。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

クロマチン運動の実験的測定と、高分子理論モデルの構築を結びつけて、クロマチンの運動を定式化することに成功した。定式化は本領域全体の目標の１つでもあり、領域に貢献する成果と考える。その他の解析についても進展しており、遺伝子発現の定式化へむけて前進した。

Strategy for Future Research Activity

(i) (A)に関連して、短い時間・空間スケールでのクロマチン運動の解析を行い、理論的に予想されているmesh sizeの実測を行う。
(ii) (B) 細胞核内の粘弾性や力を計測する方法論（磁気ピンセットの活用）の確立を継続し、クロマチン運動の物理的基盤を明らかにする。
(iii) (A)と(B)に関連して、転写活性化部位の可視化プローブを用いて、クロマチンの運動や粘弾性などとの対応を明らかにし、遺伝子発現能の定式化を行う。
(iv) (C)に関連して、(A)や(B)で得られた実験データの理論的基盤となるモデルを構築する。

Research Products

• [Int'l Joint Research] KU Leuven(ベルギー)
• [Int'l Joint Research] University of Edinburgh(英国)
• [Int'l Joint Research] KU Leuven(ベルギー)
• [Int'l Joint Research] University of Edinburgh(英国)
• [Int'l Joint Research] KU Leuven/Hasselt University(ベルギー)
• [Int'l Joint Research] Marine Biological Laboratory(米国)
• [Int'l Joint Research] Bayreuth University(ドイツ)
• [Journal Article] Entanglement in Solution of Non-concatenated Rings (2022)
  • Author(s): Sakaue Takahiro、Michieletto Davide
  • Journal Title: Topological Polymer Chemistry Volume: - Pages: 355-363
  • DOI: 10.1007/978-981-16-6807-4_22
  • Int'l Joint Research
• [Journal Article] Quantifying the mobility of chromatin during embryogenesis: Nuclear size matters (2021)
  • Author(s): Aiya K. Yesbolatova, Ritsuko Arai, Takahiro Sakaue, Akatsuki Kimura
  • Journal Title: arXiv Volume: -
  • Open Access
• [Journal Article] Sequential accumulation of dynein and its regulatory proteins at the spindle region in the Caenorhabditis elegans embryo (2021)
  • Author(s): Torisawa Takayuki、Kimura Akatsuki
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/2021.09.14.460385
  • Open Access
• [Journal Article] The extra-embryonic space is a geometric constraint regulating cell arrangement in nematodes (2021)
  • Author(s): Seirin-Lee Sungrim、Kimura Akatsuki
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/2021.06.12.448179
  • Open Access
• [Journal Article] Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates (2021)
  • Author(s): Yamamoto Tetsuya、Sakaue Takahiro、Schiessel Helmut
  • Journal Title: Nucleic Acids Res. Volume: 49 Pages: 5017-5027
  • DOI: 10.1093/nar/gkab275
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fold analysis of crumpled sheets using microcomputed tomography (2021)
  • Author(s): Hayase Yumino、Aonuma Hitoshi、Takahara Satoshi、Sakaue Takahiro、Kaneko Shun'ichi、Nakanishi Hiizu
  • Journal Title: Phys. Rev. E Volume: 104 Pages: 025005-025005
  • DOI: 10.1103/physreve.104.025005
  • Peer Reviewed
• [Journal Article] How enzymatic activity is involved in chromatin organization? (2021)
  • Author(s): Das R, Sakaue T, Shivashankar G V, Prost J, Hiraiwa T
  • Journal Title: arXiv Volume: -
  • Open Access / Int'l Joint Research
• [Journal Article] Twist dynamics and buckling instability of ring DNA: the effect of groove asymmetry and anisotropic bending (2021)
  • Author(s): Gutierrez Fosado Yair Augusto、Landuzzi Fabio、Sakaue Takahiro
  • Journal Title: Soft Matter Volume: 17 Pages: 1530-1537
  • DOI: 10.1039/d0sm01812k
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Quantifying the mobility of chromatin during embryogenesis: Nuclear size matters. (2020)
  • Author(s): Yesbolatova Aiya K.、Arai Ritsuko、Sakaue Takahiro、Akatsuki Kimura.
  • Journal Title: arXiv Volume: -
  • Open Access
• [Journal Article] Cytoplasmic streaming drifts the polarity cue and enables posteriorization of theCaenorhabditis eleganszygote at the side opposite of sperm entry (2020)
  • Author(s): Kimura Kenji、Kimura Akatsuki
  • Journal Title: Molecular Biology of the Cell Volume: 31 Pages: 1765-1773
  • DOI: 10.1091/mbc.e20-01-0058
  • Peer Reviewed / Open Access
• [Journal Article] Persistence homology of entangled rings (2020)
  • Author(s): Landuzzi Fabio、Nakamura Takenobu、Michieletto Davide、Sakaue Takahiro
  • Journal Title: Physical Review Research Volume: 2 Pages: 033529-033529
  • DOI: 10.1103/physrevresearch.2.033529
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dynamical Entanglement and Cooperative Dynamics in Entangled Solutions of Ring and Linear Polymers (2020)
  • Author(s): Michieletto Davide、Sakaue Takahiro
  • Journal Title: ACS Macro Letters Volume: 10 Pages: 129-134
  • DOI: 10.1021/acsmacrolett.0c00551
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Generation of Dynein Networks by Multi-Layered Regulation and Their Implication in Cell Division (2020)
  • Author(s): Takayuki Torisawa and Akatsuki Kimura
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 8 Pages: 1-13
  • DOI: 10.3389/fcell.2020.00022
  • Peer Reviewed / Open Access
• [Journal Article] Physics of chromatin dynamics at the 57th Biophysical Society of Japan meeting. (2020)
  • Author(s): Yuma Ito、Akatsuki Kimura
  • Journal Title: Biophysical Reviews Volume: - Pages: 265-266
  • DOI: 10.1007/s12551-020-00642-3
  • Peer Reviewed / Open Access
• [Journal Article] Transition path times in asymmetric barriers (2020)
  • Author(s): Caraglio Michele、Sakaue Takahiro、Carlon Enrico
  • Journal Title: Physical Chemistry Chemical Physics Volume: 22 Pages: 3512-3519
  • DOI: 10.1039/c9cp05659a
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Stabilization of a straight longitudinal dune under bimodal wind with large directional variation (2020)
  • Author(s): Nakao-Kusune Sachi、Sakaue Takahiro、Nishimori Hiraku、Nakanishi Hiizu
  • Journal Title: Physical Review E Volume: 101 Pages: 012903-012903
  • DOI: 10.1103/physreve.101.012903
  • Peer Reviewed
• [Journal Article] Loop extrusion drives very different dynamics for Rouse chains in bulk solutions and at interfaces (2019)
  • Author(s): Tetsuya Yamamoto, Takahiro Sakaue, and Helmut Schiessel
  • Journal Title: EPL (Europhysics Letters) Volume: 127 Pages: 38002-38002
  • DOI: 10.1209/0295-5075/127/38002
  • NAID: 120006771420
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Choice between 1- and 2-furrow cytokinesis in Caenorhabditis elegans embryos with tripolar spindles (2019)
  • Author(s): Kondo Tomo、Kimura Akatsuki
  • Journal Title: Molecular Biology of the Cell Volume: 30
  • DOI: 10.1091/mbc.e19-01-0075
  • Peer Reviewed / Open Access
• [Journal Article] Statistical physics of ring polymers based on topological volume concept (2019)
  • Author(s): Sakaue Takahiro
  • Journal Title: Reactive and Functional Polymers Volume: 134 Pages: 150-155
  • DOI: 10.1016/j.reactfunctpolym.2018.11.017
  • Peer Reviewed / Open Access
• [Journal Article] Active dynamics and spatially coherent motion in chromosomes subject to enzymatic force dipoles (2019)
  • Author(s): Put Stefanie、Sakaue Takahiro、Vanderzande Carlo
  • Journal Title: Physical Review E Volume: 99 Pages: 032421-032421
  • DOI: 10.1103/physreve.99.032421
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effect of Memory and Active Forces on Transition Path Time Distributions (2018)
  • Author(s): Carlon E.、Orland H.、Sakaue T.、Vanderzande C.
  • Journal Title: The Journal of Physical Chemistry B Volume: 122 Pages: 11186-11194
  • DOI: 10.1021/acs.jpcb.8b06379
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Topological free volume and quasi-glassy dynamics in the melt of ring polymers (2018)
  • Author(s): Sakaue Takahiro
  • Journal Title: Soft Matter Volume: 14 Pages: 7507-7515
  • DOI: 10.1039/c8sm00968f
  • Peer Reviewed / Open Access
• [Journal Article] Inferring Active Noise Characteristics from the Paired Observations of Anomalous Diffusion (2018)
  • Author(s): Saito Takuya、Sakaue Takahiro
  • Journal Title: Polymers Volume: 11 Pages: 2-2
  • DOI: 10.3390/polym11010002
  • Peer Reviewed / Open Access
• [Presentation] Quantification and formulation of the effect of nuclear size on the mobility of chromatin in the C. elegans embryo. (2022)
  • Author(s): Akatsuki Kimura
  • Organizer: The 30th Hot Spring Harbor International Symposium on Chromatin Potential in Development and Differentiation
  • Int'l Joint Research / Invited
• [Presentation] Compressing a confined DNA: from nano-channel to nano-cavity. (2021)
  • Author(s): Takahiro Sakaue
  • Organizer: CECAM workshop”Nanopore Translocation and Nanochannel confined Biopolymers: bridging theory and experiments”
  • Int'l Joint Research / Invited
• [Presentation] Chromatin dynamics in C-elegans embryo: polymer physics approach. (2021)
  • Author(s): Takahiro Sakaue
  • Organizer: Frontiers in theoretical Biophysics.
  • Int'l Joint Research / Invited
• [Presentation] Theoretical reconstitution of the nuclear size dependency of chromatin motion quantified in the Caenorhabditis elegans embryo. (2020)
  • Author(s): Kimura A.
  • Organizer: The 43rd Annual Meeting of the Molecular Biology Society of Japan
  • Invited
• [Presentation] Chromatin mobility controlled by chromatin concentration (2020)
  • Author(s): 坂上貴洋
  • Organizer: 第58回日本生物物理学会年会
  • Invited
• [Presentation] パーシスタントホモロジーを用いた環状高分子濃厚溶液の解析 (2020)
  • Author(s): 坂上貴洋
  • Organizer: TDA-MI workshop 2020
  • Invited
• [Presentation] Chromatin mobility controlled by chromatin concentration (2020)
  • Author(s): Sakaue T
  • Organizer: 2nd workshop on stochasticity and fluctuations in small systems
  • Int'l Joint Research / Invited
• [Presentation] パーシスタントホモロジーを用いた環状高分子濃厚溶液の解析２ (2020)
  • Author(s): 坂上貴洋
  • Organizer: 日本物理学会第76回年次大会
• [Presentation] Measurement of physical forces that position the nucleus at the cell center in C elegans. (2019)
  • Author(s): Kimura A
  • Organizer: Chromosome Dynamics 2019: An international symposium on chromatin and chromosome stability
  • Int'l Joint Research
• [Presentation] 細胞の構造計算と力学測定：線虫 C. elegans 胚における細胞核配置 (2019)
  • Author(s): 木村暁
  • Organizer: 「細胞を創る」研究会12.0
  • Invited
• [Presentation] Architectonics of the cell, as a crossroad of physics and genetics. (2019)
  • Author(s): Kimura A
  • Organizer: The 57th Annual Meeting of the Biophysical Society Japan
  • Invited
• [Presentation] 「力」に着目して分子の集団が細胞内の核配置を制御する仕組みを紐解く (2019)
  • Author(s): 木村暁
  • Organizer: 第92回日本生化学会大会
  • Invited
• [Presentation] クロマチンの高次構造とダイナミクス 高分子物理の視点から (2019)
  • Author(s): 坂上貴洋
  • Organizer: 第19回日本蛋白質科学会年会、第71回日本細胞生物学会大会 合同年次大会
  • Invited
• [Presentation] Structure and dynamics of chromatins: perspective from polymer physics (2019)
  • Author(s): 坂上貴洋
  • Organizer: The 57th Annual Meeting of the Biophysical Society Japan
  • Invited
• [Presentation] 遠心顕微鏡で細胞核を動かし、力を定量する (2019)
  • Author(s): 木村暁
  • Organizer: 定量生物学の会第９回年会
• [Presentation] Some Topics on Dynamics of Chromosomal Loci (2019)
  • Author(s): Sakaue T
  • Organizer: he Arctic Biophysics Meeting on Epigenetics and Chromosome Dynamics
  • Int'l Joint Research / Invited
• [Presentation] Statistical Physics of Topologically Constrained Polymers (2019)
  • Author(s): Sakaue T
  • Organizer: Polymer meets Topology
  • Int'l Joint Research / Invited
• [Presentation] 環状高分子鎖濃厚系におけるトポロジーの効果 (2019)
  • Author(s): 坂上貴洋
  • Organizer: 高分子学会講演会
  • Invited
• [Presentation] Microtubule-dependent positioning of the nucleus in the C. elegans embryo (2018)
  • Author(s): Kimura A
  • Organizer: EMBO/EMBL Symposia: Microtubules: From Atoms to Complex Systems
  • Int'l Joint Research / Invited
• [Presentation] 二光子スピニングディスク顕微鏡を用いた線虫胚発生の低退色・低毒性イメージングの可能性 (2018)
  • Author(s): 木村暁
  • Organizer: 多次元生細胞イメージング研究会
  • Invited
• [Book] Quantitative Biology - A Practical Introduction. Learning Materials in Biosciences (2022)
  • Author(s): Akatsuki Kimura
  • Total Pages: 144
  • Publisher: Springer Nature Singapore
  • ISBN: 9789811650178
• [Book] 細胞建築学入門 (2019)
  • Author(s): 木村暁
  • Total Pages: 127
  • Publisher: 工学社
  • ISBN: 9784777520954
• [Book] 定量生物学 (2018)
  • Author(s): 小林 徹也
  • Total Pages: 250
  • Publisher: 化学同人
  • ISBN: 9784759817300
• [Remarks] 国立遺伝学研究所細胞建築（木村）研究室
  • URL: https://www.nig.ac.jp/nig/ja/research/organization-top/laboratories/kimura
• [Remarks] 生命科学DOKIDOKI研究室：これから研究の話をしよう第１０回：ようこそ、細胞建築学の世界へ
  • URL: https://www.terumozaidan.or.jp/labo/future/10/index.html
• [Remarks] 青山学院大学理工学部物理科学科坂上研究室
  • URL: http://www.agnes.aoyama.ac.jp/phys-math/sakaue/
• [Remarks] ２つに分裂するか、３つに分裂するか、それが問題だ
  • URL: https://www.nig.ac.jp/nig/ja/2019/04/research-highlights_ja/rh20190304.html
• [Remarks] 物理計測と理論モデル構築によるクロマチンポテンシャルの理解
  • URL: http://www.nibb.ac.jp/potentia/member/kimuraa.html
• [Remarks] 国立遺伝学研究所細胞建築研究室
  • URL: http://cellarchlab.galaxy.bindcloud.jp/home_jp.html