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  1. Article ; Online: Enhancer dynamics: Unraveling the mechanism of transcriptional bursting.

    Fukaya, Takashi

    Science advances

    2023  Volume 9, Issue 31, Page(s) eadj3366

    Abstract: Transcriptional bursting is a prevalent feature of gene expression. The transient assembly of transcription factor clusters at regulatory DNAs is critical to control bursting dynamics. ...

    Abstract Transcriptional bursting is a prevalent feature of gene expression. The transient assembly of transcription factor clusters at regulatory DNAs is critical to control bursting dynamics.
    MeSH term(s) Humans ; Animals ; Transcription, Genetic ; Enhancer Elements, Genetic ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adj3366
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  2. Article ; Online: Dynamic regulation of anterior-posterior patterning genes in living Drosophila embryos.

    Fukaya, Takashi

    Current biology : CB

    2021  Volume 31, Issue 10, Page(s) 2227–2236.e6

    Abstract: Expression of the gap and pair-rule genes plays an essential role in body segmentation during Drosophila embryogenesis. ...

    Abstract Expression of the gap and pair-rule genes plays an essential role in body segmentation during Drosophila embryogenesis.
    MeSH term(s) Animals ; Body Patterning/genetics ; Drosophila/embryology ; Drosophila/genetics ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics ; Transcription Factors/metabolism ; Transcriptional Activation
    Chemical Substances Drosophila Proteins ; Homeodomain Proteins ; Transcription Factors
    Language English
    Publishing date 2021-03-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2021.02.050
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3208: Show issues Location:
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  3. Article ; Online: Regulatory landscape of enhancer-mediated transcriptional activation.

    Kawasaki, Koji / Fukaya, Takashi

    Trends in cell biology

    2024  

    Abstract: Enhancers are noncoding regulatory elements that instruct spatial and temporal specificity of gene transcription in response to a variety of intrinsic and extrinsic signals during development. Although it has long been postulated that enhancers ... ...

    Abstract Enhancers are noncoding regulatory elements that instruct spatial and temporal specificity of gene transcription in response to a variety of intrinsic and extrinsic signals during development. Although it has long been postulated that enhancers physically interact with target promoters through the formation of stable loops, recent studies have changed this static view: sequence-specific transcription factors (TFs) and coactivators are dynamically recruited to enhancers and assemble so-called transcription hubs. Dynamic assembly of transcription hubs appears to serve as a key scaffold to integrate regulatory information encoded by surrounding genome and biophysical properties of transcription machineries. In this review, we outline emerging new models of transcriptional regulation by enhancers and discuss future perspectives.
    Language English
    Publishing date 2024-02-13
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 30122-x
    ISSN 1879-3088 ; 0962-8924
    ISSN (online) 1879-3088
    ISSN 0962-8924
    DOI 10.1016/j.tcb.2024.01.008
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  4. Article ; Online: Functional coordination between transcription factor clustering and gene activity.

    Kawasaki, Koji / Fukaya, Takashi

    Molecular cell

    2023  Volume 83, Issue 10, Page(s) 1605–1622.e9

    Abstract: The prevailing view of metazoan gene regulation is that transcription is facilitated through the formation of static activator complexes at distal regulatory regions. Here, we employed quantitative single-cell live-imaging and computational analysis to ... ...

    Abstract The prevailing view of metazoan gene regulation is that transcription is facilitated through the formation of static activator complexes at distal regulatory regions. Here, we employed quantitative single-cell live-imaging and computational analysis to provide evidence that the dynamic assembly and disassembly process of transcription factor (TF) clusters at enhancers is a major source of transcriptional bursting in developing Drosophila embryos. We further show that the regulatory connectivity between TF clustering and burst induction is highly regulated through intrinsically disordered regions (IDRs). Addition of a poly-glutamine tract to the maternal morphogen Bicoid demonstrated that extended IDR length leads to ectopic TF clustering and burst induction from its endogenous target genes, resulting in defects in body segmentation during embryogenesis. Moreover, we successfully visualized the presence of "shared" TF clusters during the co-activation of two distant genes, which provides a concrete molecular explanation for the newly proposed "topological operon" hypothesis in metazoan gene regulation.
    MeSH term(s) Animals ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Enhancer Elements, Genetic ; Gene Expression Regulation, Developmental ; Drosophila/genetics
    Chemical Substances Transcription Factors ; Drosophila Proteins
    Language English
    Publishing date 2023-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2023.04.018
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    Zs.A 5055: Show issues Location:
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  5. Article: Absolute reliability of Young's modulus of the soleus muscle and Achilles tendon measured using shear wave elastography in healthy young males.

    Miyasaka, Hayato / Ebihara, Bungo / Fukaya, Takashi / Mutsuzaki, Hirotaka

    Asia-Pacific journal of sports medicine, arthroscopy, rehabilitation and technology

    2024  Volume 37, Page(s) 1–7

    Abstract: Background: Stiffness of the soleus muscle (SOL) and Achilles tendon (AT) are associated with Achilles tendinitis and medial tibial stress syndrome. Therefore, reliable SOL and AT stiffness measurements are important for monitoring clinical progress. ... ...

    Abstract Background: Stiffness of the soleus muscle (SOL) and Achilles tendon (AT) are associated with Achilles tendinitis and medial tibial stress syndrome. Therefore, reliable SOL and AT stiffness measurements are important for monitoring clinical progress. However, little is known about the absolute reliability of the stiffness measurements of SOL and AT in different ankle positions. This study aimed to determine the absolute reliability of the Young's modulus measurements of the SOL and AT in different ankle positions in healthy young males.
    Methods: This study included 33 healthy young males. SOL and AT stiffnesses were measured using Young's modulus and shear-wave elastography (SWE). Measurements were taken while the participants were kneeling, with their knees flexed to 90°, and the upper body supported by a table. Ultrasound images were recorded at ankle dorsiflexion angles of -10°, 0°, and 10°. The same measurements were repeated 15 min after the first measurement. Bland-Altman plots were used to verify the type or amount of error and 95 % confidence interval of the minimal detectable change (MDC
    Results: Bland-Altman plots identified that there was no fixed or proportional bias and that there was good agreement between the first- and second-time measurements of the SOL and AT, respectively, among all angles. The MDC
    Conclusion: Young's modulus measurements of the SOL and AT using SWE can be used to quantify elastic properties with high confidence. Clinically, assessing changes in the Young's moduli of the SOL and AT using SWE may help determine the effectiveness of interventions.
    Language English
    Publishing date 2024-04-20
    Publishing country Singapore
    Document type Journal Article
    ZDB-ID 2817806-3
    ISSN 2214-6873
    ISSN 2214-6873
    DOI 10.1016/j.asmart.2024.04.001
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  6. Article ; Online: Molecular architecture of enhancer-promoter interaction.

    Hamamoto, Kota / Fukaya, Takashi

    Current opinion in cell biology

    2022  Volume 74, Page(s) 62–70

    Abstract: Temporal and spatial specificity of gene expression is highly regulated through a rich milieu of regulatory DNAs embedded in the genome. Enhancers represent a major class of regulatory DNAs that consist of a cluster of binding sites for sequence-specific ...

    Abstract Temporal and spatial specificity of gene expression is highly regulated through a rich milieu of regulatory DNAs embedded in the genome. Enhancers represent a major class of regulatory DNAs that consist of a cluster of binding sites for sequence-specific transcription factors and are thought to facilitate recruitment of transcription machinery to their target promoters from remote locations. It has been over four decades since the discovery of prototypic simian virus 40 enhancer, yet the nature of enhancer-promoter interaction still remains an outstanding mystery in gene regulation. The aim of this review is to comprehensively overview molecular mechanisms underlying enhancer-promoter interaction including the roles of looping factors, higher-order genome topology, and dynamic clustering of transcription apparatus within a nucleus. We propose that cooperative interplay between 'looping' and 'hub' permits distal enhancers to specifically and dynamically modulate target gene expression over large distances.
    MeSH term(s) Binding Sites ; DNA ; Enhancer Elements, Genetic/genetics ; Gene Expression Regulation ; Promoter Regions, Genetic ; Transcription Factors/metabolism ; Transcription, Genetic
    Chemical Substances Transcription Factors ; DNA (9007-49-2)
    Language English
    Publishing date 2022-02-12
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2022.01.003
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    Zs.A 2963: Show issues Location:
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  7. Article ; Online: Dynamic interplay between non-coding enhancer transcription and gene activity in development.

    Hamamoto, Kota / Umemura, Yusuke / Makino, Shiho / Fukaya, Takashi

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 826

    Abstract: Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devise a live-imaging system that permits simultaneous visualization of gene activity along ... ...

    Abstract Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devise a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at single-cell resolution in Drosophila. Quantitative image analysis reveals that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrate that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of a transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.
    MeSH term(s) Animals ; Regulatory Sequences, Nucleic Acid ; DNA, Intergenic/genetics ; Drosophila/genetics ; Gene Editing ; RNA Polymerase II/genetics
    Chemical Substances DNA, Intergenic ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2023-02-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36485-1
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  8. Article ; Online: Relationship between the Young's Modulus of the Achilles Tendon and Ankle Dorsiflexion Angle at Maximum Squat Depth in Healthy Young Males.

    Miyasaka, Hayato / Ebihara, Bungo / Fukaya, Takashi / Mutsuzaki, Hirotaka

    Medicina (Kaunas, Lithuania)

    2023  Volume 59, Issue 6

    Abstract: Background and ... ...

    Abstract Background and Objective
    MeSH term(s) Male ; Humans ; Elastic Modulus ; Achilles Tendon/diagnostic imaging ; Ankle ; Cross-Sectional Studies ; Elasticity Imaging Techniques
    Language English
    Publishing date 2023-06-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2188113-3
    ISSN 1648-9144 ; 1010-660X
    ISSN (online) 1648-9144
    ISSN 1010-660X
    DOI 10.3390/medicina59061105
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  9. Article ; Online: Sway and Acceleration Changes of the Center of Mass during Walking Stance Phase before and after Total Knee Arthroplasty.

    Fukaya, Takashi / Mutsuzaki, Hirotaka / Mori, Koichi

    Geriatrics (Basel, Switzerland)

    2022  Volume 8, Issue 1

    Abstract: Elucidating the sway and changes in the acceleration of center of mass (COM) during walking is important for effective gait training and rehabilitation. The objective of this study was to verify the improvement in gait before and after total knee ... ...

    Abstract Elucidating the sway and changes in the acceleration of center of mass (COM) during walking is important for effective gait training and rehabilitation. The objective of this study was to verify the improvement in gait before and after total knee arthroplasty (TKA) from COM sway and the changes in the acceleration of COM during the stance phase of walking. This study included 13 patients (1 male and 12 females) with medial knee osteoarthritis who were hospitalized for TKA. The COM sway during the stance phase of walking was evaluated using root mean square (RMS) normalized by walking speed, and the changes in acceleration were further verified. Lateral and vertical RMS showed significant differences between preoperative and postoperative states and demonstrated low values after TKA. The lateral acceleration at the latter part of the early stance phase demonstrated a significant difference between preoperative and postoperative states. A significant difference was also observed in the lateral acceleration in the late stance phase between the two groups. Improvement in pain and alignment after TKA reduced the lateral sway of COM and the changes in acceleration during the gait stance phase, which is speculated to lead to improvement in gait and prevention of falls.
    Language English
    Publishing date 2022-12-24
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2308-3417
    ISSN (online) 2308-3417
    DOI 10.3390/geriatrics8010002
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  10. Article ; Online: Dynamic modulation of enhancer responsiveness by core promoter elements in living Drosophila embryos.

    Yokoshi, Moe / Kawasaki, Koji / Cambón, Manuel / Fukaya, Takashi

    Nucleic acids research

    2022  Volume 50, Issue 1, Page(s) 92–107

    Abstract: Regulatory interactions between enhancers and core promoters are fundamental for the temporal and spatial specificity of gene expression in development. The central role of core promoters is to initiate productive transcription in response to enhancer's ... ...

    Abstract Regulatory interactions between enhancers and core promoters are fundamental for the temporal and spatial specificity of gene expression in development. The central role of core promoters is to initiate productive transcription in response to enhancer's activation cues. However, it has not been systematically assessed how individual core promoter elements affect the induction of transcriptional bursting by enhancers. Here, we provide evidence that each core promoter element differentially modulates functional parameters of transcriptional bursting in developing Drosophila embryos. Quantitative live imaging analysis revealed that the timing and the continuity of burst induction are common regulatory steps on which core promoter elements impact. We further show that the upstream TATA also affects the burst amplitude. On the other hand, Inr, MTE and DPE mainly contribute to the regulation of the burst frequency. Genome editing analysis of the pair-rule gene fushi tarazu revealed that the endogenous TATA and DPE are both essential for its correct expression and function during the establishment of body segments in early embryos. We suggest that core promoter elements serve as a key regulatory module in converting enhancer activity into transcription dynamics during animal development.
    MeSH term(s) Animals ; Drosophila melanogaster ; Embryo, Nonmammalian/metabolism ; Enhancer Elements, Genetic ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Transcriptome
    Language English
    Publishing date 2022-01-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkab1177
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