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  1. 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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  2. 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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  3. 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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    Zs.A 1067: Show issues Location:
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  4. Article ; Online: Involvement of glycogen metabolism in circadian control of UV resistance in cyanobacteria.

    Kawasaki, Koji / Iwasaki, Hideo

    PLoS genetics

    2020  Volume 16, Issue 11, Page(s) e1009230

    Abstract: Most organisms harbor circadian clocks as endogenous timing systems in order to adapt to daily environmental changes, such as exposure to ultraviolet (UV) light. It has been hypothesized that the circadian clock evolved to prevent UV-sensitive activities, ...

    Abstract Most organisms harbor circadian clocks as endogenous timing systems in order to adapt to daily environmental changes, such as exposure to ultraviolet (UV) light. It has been hypothesized that the circadian clock evolved to prevent UV-sensitive activities, such as DNA replication and cell division, during the daytime. Indeed, circadian control of UV resistance has been reported in several eukaryotic organisms, from algae to higher organisms, although the underlying mechanisms remain unknown. Here, we demonstrate that the unicellular cyanobacterium Synechococcus elongatus PCC 7942 exhibits a circadian rhythm in resistance to UV-C and UV-B light, which is higher during subjective dawn and lower during subjective dusk. Nullification of the clock gene cluster kaiABC or the DNA-photolyase phr abolished rhythmicity with constitutively lower resistance to UV-C light, and amino acid substitutions of KaiC altered the period lengths of the UV-C resistance rhythm. In order to elucidate the molecular mechanism underlying the circadian regulation of UV-C resistance, transposon insertion mutants that alter UV-C resistance were isolated. Mutations to the master circadian output mediator genes sasA and rpaA and the glycogen degradation enzyme gene glgP abolished circadian rhythms of UV-C resistance with constitutively high UV-C resistance. Combining these results with further experiments using ATP synthesis inhibitor and strains with modified metabolic pathways, we showed that UV-C resistance is weakened by directing more metabolic flux from the glycogen degradation to catabolic pathway such as oxidative pentose phosphate pathway and glycolysis. We suggest glycogen-related metabolism in the dark affects circadian control in UV sensitivity, while the light masks this effect through the photolyase function.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Circadian Rhythm Signaling Peptides and Proteins/genetics ; Circadian Rhythm Signaling Peptides and Proteins/metabolism ; DNA Transposable Elements/genetics ; Deoxyribodipyrimidine Photo-Lyase/genetics ; Deoxyribodipyrimidine Photo-Lyase/metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial/genetics ; Glycogen/metabolism ; Metabolic Networks and Pathways/genetics ; Mutation ; Photoperiod ; Radiation Tolerance/genetics ; Synechococcus/physiology ; Synechococcus/radiation effects ; Ultraviolet Rays/adverse effects
    Chemical Substances Bacterial Proteins ; Circadian Rhythm Signaling Peptides and Proteins ; DNA Transposable Elements ; Glycogen (9005-79-2) ; Deoxyribodipyrimidine Photo-Lyase (EC 4.1.99.3)
    Language English
    Publishing date 2020-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009230
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  5. Article ; Online: Impact of H

    Yabuta, Keisho / Futamura, Haruka / Kawasaki, Koji / Sugiyama, Hirokazu

    Journal of pharmaceutical sciences

    2020  Volume 109, Issue 9, Page(s) 2767–2773

    Abstract: As part of manufacturing a sterile drug product, we quantified the impact of ... ...

    Abstract As part of manufacturing a sterile drug product, we quantified the impact of H
    MeSH term(s) Decontamination ; Hydrogen Peroxide ; Models, Theoretical ; Pharmaceutical Preparations ; Polymers
    Chemical Substances Pharmaceutical Preparations ; Polymers ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2020-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3151-3
    ISSN 1520-6017 ; 0022-3549
    ISSN (online) 1520-6017
    ISSN 0022-3549
    DOI 10.1016/j.xphs.2020.05.024
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  6. Article ; Online: Association of low fetuin-A levels with periodontitis in community-dwelling adults.

    Furugen, Reiko / Kawasaki, Koji / Kitamura, Masayasu / Maeda, Takahiro / Saito, Toshiyuki / Hayashida, Hideaki

    Journal of oral science

    2020  Volume 62, Issue 1, Page(s) 67–69

    Abstract: Fetuin-A is a liver-secreted glycoprotein isolated from fetal bovine serum. Recent reports of its several pathological functions suggest an association between fetuin-A and systemic diseases. This study therefore examined the correlation between serum ... ...

    Abstract Fetuin-A is a liver-secreted glycoprotein isolated from fetal bovine serum. Recent reports of its several pathological functions suggest an association between fetuin-A and systemic diseases. This study therefore examined the correlation between serum fetuin-A level and periodontal status. Data from 356 middle-aged and elderly adults who underwent health examinations in Goto, Japan, during the period from 2008 through 2010 were analyzed. Systemic and periodontal measurements were recorded, and serum fetuin-A level was determined by using an enzyme-linked immunosorbent assay. Fetuin-A levels for participants with moderate to severe periodontitis were significantly lower than those for participants with no or mild periodontitis. Additionally, fetuin-A level negatively correlated with periodontal clinical attachment loss. Moderate to severe periodontitis was significantly correlated with low serum fetuin-A levels (odds ratio, 1.69; 95% confidence interval, 1.01-2.69) in logistic regression analysis. Low serum fetuin-A level was correlated with worse periodontal status and could thus potentially serve as a marker of periodontitis.
    MeSH term(s) Adult ; Aged ; Humans ; Independent Living ; Japan ; Middle Aged ; Periodontal Attachment Loss ; Periodontitis ; alpha-2-HS-Glycoprotein
    Chemical Substances alpha-2-HS-Glycoprotein
    Language English
    Publishing date 2020-01-29
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1434462-2
    ISSN 1880-4926 ; 1343-4934
    ISSN (online) 1880-4926
    ISSN 1343-4934
    DOI 10.2334/josnusd.18-0282
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    Zs.A 189: Show issues Location:
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  7. Article: Effects of ion-releasing tooth-coating material on demineralization of bovine tooth enamel.

    Kawasaki, Koji / Kambara, Masaki

    International journal of dentistry

    2014  Volume 2014, Page(s) 463149

    Abstract: We compared the effect of a novel ion-releasing tooth-coating material that contained S-PRG (surface-reaction type prereacted glass-ionomer) filler to that of non-S-PRG filler and nail varnish on the demineralization of bovine enamel subsurface lesions. ... ...

    Abstract We compared the effect of a novel ion-releasing tooth-coating material that contained S-PRG (surface-reaction type prereacted glass-ionomer) filler to that of non-S-PRG filler and nail varnish on the demineralization of bovine enamel subsurface lesions. The demineralization process of bovine enamel was examined using quantitative light-induced fluorescence (QLF) and electron probe microanalyzer (EPMA) measurement. Ion concentrations in demineralizing solution were measured using inductively coupled plasma atomic (ICP) emission spectrometry and an ion electrode. The nail varnish group and the non-S-PRG filler group showed linear demineralization. Although the nail varnish group and the non-S-PRG filler group showed linear demineralization, the S-PRG filler group did not. Further, plane-scanning by EPMA analysis in the S-PRG filler group showed no changes in Ca ion distribution, and F ions showed peak levels on the surface of enamel specimens. Most ions in the demineralizing solution were present at higher concentrations in the S-PRG filler group than in the other two groups. In conclusion, only the S-PRG filler-containing tooth-coating material released ions and inhibited demineralization around the coating.
    Language English
    Publishing date 2014-01-21
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2546524-7
    ISSN 1687-8736 ; 1687-8728
    ISSN (online) 1687-8736
    ISSN 1687-8728
    DOI 10.1155/2014/463149
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  8. Article ; Online: Design-oriented regression models for H

    Yabuta, Keisho / Futamura, Haruka / Kawasaki, Koji / Hirao, Masahiko / Sugiyama, Hirokazu

    International journal of pharmaceutics

    2018  Volume 548, Issue 1, Page(s) 466–473

    Abstract: We developed regression models for designing rapid and effective ... ...

    Abstract We developed regression models for designing rapid and effective H
    MeSH term(s) Decontamination/methods ; Drug Compounding ; Hydrogen Peroxide/chemistry ; Models, Theoretical ; Oxidants/chemistry ; Regression Analysis ; Sterilization
    Chemical Substances Oxidants ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2018-06-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2018.06.055
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  9. Article: [Not Available].

    Jin, Koichiro / Kawasaki, Koji / Doi, Takashi / Uene, Masako / Kanbara, Masaki

    Nihon koshu eisei zasshi] Japanese journal of public health

    2015  Volume 62, Issue 12, Page(s) 739

    Language Japanese
    Publishing date 2015
    Publishing country Japan
    Document type Letter
    ZDB-ID 45044-3
    ISSN 0546-1766
    ISSN 0546-1766
    DOI 10.11236/jph.62.12_739
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    Zs.A 3721: Show issues Location:
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  10. Article: [The effects of oral health ordinances and legislation promoting dental and oral health on community-based dental and oral health organizations].

    Jin, Koichiro / Kawasaki, Koji / Doi, Takashi / Uene, Masako / Kanbara, Masaki

    Nihon koshu eisei zasshi] Japanese journal of public health

    2015  Volume 62, Issue 6, Page(s) 294–299

    MeSH term(s) Health Policy ; Health Promotion/organization & administration ; Humans ; Japan ; Oral Health/legislation & jurisprudence ; Oral Health/trends
    Language Japanese
    Publishing date 2015
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 45044-3
    ISSN 0546-1766
    ISSN 0546-1766
    DOI 10.11236/jph.62.6_294
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