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Molecular cell 20건

  1. [해외논문]   PARP1 and Sox2: An Unlikely Team of Pioneers to Conquer the Nucleosome   SCI SCIE

    Gaullier, Guillaume (Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, CO 80309, USA ) , Luger, Karolin (Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, CO 80309, USA)
    Molecular cell v.65 no.4 ,pp. 581 - 582 , 2017 , 1097-2765 ,

    초록

    In this issue of Molecular Cell , demonstrate that the pioneer transcription factor Sox2 requires PARP1 to bind to a subset of its recognition motifs, which are located within nucleosomes across the genome.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  2. [해외논문]   Expanding the CRISPR Toolbox: Targeting RNA with Cas13b   SCI SCIE

    Barrangou, Rodolphe (Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695, USA ) , Gersbach, Charles A. (Department of Biomedical Engineering, Center for Genomic & Computational Biology, Duke University, Durham, NC 27708, USA)
    Molecular cell v.65 no.4 ,pp. 582 - 584 , 2017 , 1097-2765 ,

    초록

    In this issue of Molecular Cell , unearth Cas13b from type VI-B CRISPR-Cas immune systems and characterize its RNA-guided, RNA-targeting activity, including regulation by the novel co-factors Csx27 and Csx28, as well as non-specific collateral RNA damage.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  3. [해외논문]   Jekyll & Hyde: The Other Life of the Death Ligand TRAIL   SCI SCIE

    Lalaoui, Najoua (The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia ) , Silke, John (The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia)
    Molecular cell v.65 no.4 ,pp. 585 - 587 , 2017 , 1097-2765 ,

    초록

    and provide more insights into the non-apoptotic function of the FADD/caspase-8 duo in TRAIL signaling.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  4. [해외논문]   Catalytic-Independent Functions of PARP-1 Determine Sox2 Pioneer Activity at Intractable Genomic Loci   SCI SCIE

    Liu, Ziying (The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences and The Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8511, USA ) , Kraus, W. Lee (The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences and The Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8511, USA)
    Molecular cell v.65 no.4 ,pp. 589 - 603.e9 , 2017 , 1097-2765 ,

    초록

    Summary Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity. PARP-1-dependent Sox2-binding sites reside in euchromatic regions of the genome with relatively high nucleosome occupancy and low co-occupancy by other transcription factors. PARP-1 stabilizes Sox2 binding to nucleosomes at suboptimal sites through cooperative interactions on DNA. Our results define intrinsic and extrinsic features that determine Sox2 pioneer activity. The conditional pioneer activity observed with Sox2 at a subset of binding sites may be a key feature of other pioneer TFs operating at intractable genomic loci. Highlights A subset of biologically important Sox2 genomic binding sites in mESCs requires PARP-1 PARP-1-dependent Sox2-binding sites reside in regions of intractable euchromatin These Sox2 sites have a specific nucleosome rotational positioning of the Sox motif PARP-1 stabilizes Sox2 binding through cooperative interactions on DNA Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [해외논문]   Systematic Investigation of Transcription Factor Activity in the Context of Chromatin Using Massively Parallel Binding and Expression Assays   SCI SCIE

    Levo, Michal (Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel ) , Avnit-Sagi, Tali (Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel ) , Lotan-Pompan, Maya (Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel ) , Kalma, Yael (Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel ) , Weinberger, Adina (Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel ) , Yakhini, Zohar (Computer Science Department, Technion, Haifa 3200003, Israel ) , Segal, Eran (Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel)
    Molecular cell v.65 no.4 ,pp. 604 - 617.e6 , 2017 , 1097-2765 ,

    초록

    Summary Precise gene expression patterns are established by transcription factor (TFs) binding to regulatory sequences. While these events occur in the context of chromatin, our understanding of how TF-nucleosome interplay affects gene expression is highly limited. Here, we present an assay for high-resolution measurements of both DNA occupancy and gene expression on large-scale libraries of systematically designed regulatory sequences. Our assay reveals occupancy patterns at the single-cell level. It provides an accurate quantification of the fraction of the population bound by a nucleosome and captures distinct, even adjacent, TF binding events. By applying this assay to over 1,500 promoter variants in yeast, we reveal pronounced differences in the dependency of TF activity on chromatin and classify TFs by their differential capacity to alter chromatin and promote expression. We further demonstrate how different regulatory sequences give rise to nucleosome-mediated TF collaborations that quantitatively account for the resulting expression. Highlights Parallel expression and occupancy measurements reveal TF-nucleosome interplay Pronounced differences in transcription factors (TFs) sensitivity to chromatin Specific combinations of TF sites give rise to nucleosome-mediated collaborations Properties of nucleosome-based collaborations can quantitatively shape expression Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  6. [해외논문]   Cas13b Is a Type VI-B CRISPR-Associated RNA-Guided RNase Differentially Regulated by Accessory Proteins Csx27 and Csx28  

    Smargon, Aaron A. , Cox, David B.T. , Pyzocha, Neena K. , Zheng, Kaijie , Slaymaker, Ian M. , Gootenberg, Jonathan S. , Abudayyeh, Omar A. , Essletzbichler, Patrick , Shmakov, Sergey , Makarova, Kira S. , Koonin, Eugene V. , Zhang, Feng
    Molecular cell v.65 no.4 ,pp. 618 - 630.e7 , 2017 , 1097-2765 ,

    초록

    Summary Precise gene expression patterns are established by transcription factor (TFs) binding to regulatory sequences. While these events occur in the context of chromatin, our understanding of how TF-nucleosome interplay affects gene expression is highly limited. Here, we present an assay for high-resolution measurements of both DNA occupancy and gene expression on large-scale libraries of systematically designed regulatory sequences. Our assay reveals occupancy patterns at the single-cell level. It provides an accurate quantification of the fraction of the population bound by a nucleosome and captures distinct, even adjacent, TF binding events. By applying this assay to over 1,500 promoter variants in yeast, we reveal pronounced differences in the dependency of TF activity on chromatin and classify TFs by their differential capacity to alter chromatin and promote expression. We further demonstrate how different regulatory sequences give rise to nucleosome-mediated TF collaborations that quantitatively account for the resulting expression. Highlights Parallel expression and occupancy measurements reveal TF-nucleosome interplay Pronounced differences in transcription factors (TFs) sensitivity to chromatin Specific combinations of TF sites give rise to nucleosome-mediated collaborations Properties of nucleosome-based collaborations can quantitatively shape expression Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  7. [해외논문]   Cas13b Is a Type VI-B CRISPR-Associated RNA-Guided RNase Differentially Regulated by Accessory Proteins Csx27 and Csx28   SCI SCIE

    Smargon, Aaron A. (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Cox, David B.T. (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Pyzocha, Neena K. (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Zheng, Kaijie (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Slaymaker, Ian M. (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Gootenberg, Jonathan S. (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Abudayyeh, Omar A. (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Essletzbichler, Patrick (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA ) , Shmakov, Sergey (Skolkovo Institute of Science and Technology, Skolkovo 143025, Russia ) , Makarova, Kira S. (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA ) , Koonin, Eugene V. (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA ) , Zhang, Feng (Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA)
    Molecular cell v.65 no.4 ,pp. 618 - 630.e7 , 2017 , 1097-2765 ,

    초록

    Summary CRISPR-Cas adaptive immune systems defend microbes against foreign nucleic acids via RNA-guided endonucleases. Using a computational sequence database mining approach, we identify two class 2 CRISPR-Cas systems (subtype VI-B) that lack Cas1 and Cas2 and encompass a single large effector protein, Cas13b, along with one of two previously uncharacterized associated proteins, Csx27 and Csx28. We establish that these CRISPR-Cas systems can achieve RNA interference when heterologously expressed. Through a combination of biochemical and genetic experiments, we show that Cas13b processes its own CRISPR array with short and long direct repeats, cleaves target RNA, and exhibits collateral RNase activity. Using an E. coli essential gene screen, we demonstrate that Cas13b has a double-sided protospacer-flanking sequence and elucidate RNA secondary structure requirements for targeting. We also find that Csx27 represses, whereas Csx28 enhances, Cas13b-mediated RNA interference. Characterization of these CRISPR systems creates opportunities to develop tools to manipulate and monitor cellular transcripts. Highlights CRISPR-Cas13b is a class 2 type VI-B CRISPR system lacking Cas1 and Cas2 Cas13b is a CRISPR-associated RNA-guided RNase with two crRNA variants Csx27 represses, whereas Csx28 enhances, Cas13b activity Cas13b RNA targeting is dependent on a double-sided PFS and RNA accessibility Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  8. [해외논문]   Comparative Analysis of Single-Cell RNA Sequencing Methods   SCI SCIE

    Ziegenhain, Christoph (Anthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians University, Großhaderner Straße 2, 82152 Martinsried, Germany ) , Vieth, Beate (Anthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians University, Großhaderner Straße 2, 82152 Martinsried, Germany ) , Parekh, Swati (Anthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians University, Großhaderner Straße 2, 82152 Martinsried, Germany ) , Reinius, Bjö (Ludwig Institute for Cancer Research, Box 240, 171 77 Stockholm, Sweden ) , rn (CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain ) , Guillaumet-Adkins, Amy (Department of Biology II and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University, Großhaderner Straße 2, 82152 Martinsried, Germany ) , Smets, Martha (Department of Biology II and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University, Großhaderner Straße 2, 82152 Martinsried, Germany ) , Leonhardt, Heinrich (CNAG-CRG, Centre for Genomic) , Heyn, Holger , Hellmann, Ines , Enard, Wolfgang
    Molecular cell v.65 no.4 ,pp. 631 - 643.e4 , 2017 , 1097-2765 ,

    초록

    Summary Single-cell RNA sequencing (scRNA-seq) offers new possibilities to address biological and medical questions. However, systematic comparisons of the performance of diverse scRNA-seq protocols are lacking. We generated data from 583 mouse embryonic stem cells to evaluate six prominent scRNA-seq methods: CEL-seq2, Drop-seq, MARS-seq, SCRB-seq, Smart-seq, and Smart-seq2. While Smart-seq2 detected the most genes per cell and across cells, CEL-seq2, Drop-seq, MARS-seq, and SCRB-seq quantified mRNA levels with less amplification noise due to the use of unique molecular identifiers (UMIs). Power simulations at different sequencing depths showed that Drop-seq is more cost-efficient for transcriptome quantification of large numbers of cells, while MARS-seq, SCRB-seq, and Smart-seq2 are more efficient when analyzing fewer cells. Our quantitative comparison offers the basis for an informed choice among six prominent scRNA-seq methods, and it provides a framework for benchmarking further improvements of scRNA-seq protocols. Highlights The study represents the most comprehensive comparison of scRNA-seq protocols Power simulations quantify the effect of sensitivity and precision on cost efficiency The study offers an informed choice among six prominent scRNA-seq methods The study provides a framework for benchmarking future protocol improvements Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  9. [해외논문]   Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery   SCI SCIE

    Choy, Meng S. (Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA ) , Li, Yang (Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA ) , Machado, Luciana E.S.F. (Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA ) , Kunze, Micha B.A. (Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark, Brown University, Providence, RI 02912, USA ) , Connors, Christopher R. (Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA ) , Wei, Xingyu (Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA ) , Lindorff-Larsen, Kresten (Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark, Brown University, Providence, RI 02912, USA ) , Page, Rebecca (Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA ) , Peti, Wolfgang (Department of Molecular Pharmacology, Physiology and Biotechnology, Brown Univ)
    Molecular cell v.65 no.4 ,pp. 644 - 658.e5 , 2017 , 1097-2765 ,

    초록

    Summary Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Highlights Distinct dynamic timescales underlie catalysis versus allosteric control in PTP1B Fast and slow timescale motions are uncoupled in PTP1B The rigid CH/π switch is critical for the opening and closing of the WPD loop Fast timescale motions, via helix α7, allow for PTP1B allosteric control Graphical Abstract [DISPLAY OMISSION]

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  10. [해외논문]   Stable Heritable Germline Silencing Directs Somatic Silencing at an Endogenous Locus   SCI SCIE

    Minkina, Olga (Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA ) , Hunter, Craig P. (Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA)
    Molecular cell v.65 no.4 ,pp. 659 - 670.e5 , 2017 , 1097-2765 ,

    초록

    Summary The importance of transgenerationally inherited epigenetic states to organismal fitness remains unknown as well-documented examples are often not amenable to mechanistic analysis or rely on artificial reporter loci. Here we describe an induced silenced state at an endogenous locus that persists, at 100% transmission without selection, for up to 13 generations. This unusually persistent silencing enables a detailed molecular genetic analysis of an inherited epigenetic state. We find that silencing is dependent on germline nuclear RNAi factors and post-transcriptional mechanisms. Consistent with these later observations, inheritance does not require the silenced locus, and we provide genetic evidence that small RNAs embody the inherited silencing signal. Notably, heritable germline silencing directs somatic epigenetic silencing. Somatic silencing does not require somatic nuclear RNAi but instead requires both maternal germline nuclear RNAi and chromatin-modifying activity. Coupling inherited germline silencing to somatic silencing may enable selection for physiologically important traits. Highlights A multi-copy array of the region upstream of sid-1 silences sid-1 Epigenetic sid-1 silencing is transmitted to all progeny for up to 13 generations Small RNAs embody the inherited silencing signal in the germline Chromatin-modifying enzymes contribute to sid-1 silencing in the soma Graphical Abstract [DISPLAY OMISSION]

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    Fig. 1 이미지

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