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  1. Article ; Online: Kinetic Proofreading.

    Boeger, Hinrich

    Annual review of biochemistry

    2022  Volume 91, Page(s) 423–447

    Abstract: Biochemistry and molecular biology rely on the recognition of structural complementarity between molecules. Molecular interactions must be both quickly reversible, i.e., tenuous, and specific. How the cell reconciles these conflicting demands is the ... ...

    Abstract Biochemistry and molecular biology rely on the recognition of structural complementarity between molecules. Molecular interactions must be both quickly reversible, i.e., tenuous, and specific. How the cell reconciles these conflicting demands is the subject of this article. The problem and its theoretical solution are discussed within the wider theoretical context of the thermodynamics of stochastic processes (stochastic thermodynamics). The solution-an irreversible reaction cycle that decreases internal error at the expense of entropy export into the environment-is shown to be widely employed by biological processes that transmit genetic and regulatory information.
    MeSH term(s) Kinetics ; Stochastic Processes ; Thermodynamics
    Language English
    Publishing date 2022-04-01
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 207924-0
    ISSN 1545-4509 ; 0066-4154
    ISSN (online) 1545-4509
    ISSN 0066-4154
    DOI 10.1146/annurev-biochem-040320-103630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Nucleosomal proofreading of activator-promoter interactions.

    Shelansky, Robert / Boeger, Hinrich

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 5, Page(s) 2456–2461

    Abstract: Specificity in transcriptional regulation is imparted by transcriptional activators that bind to specific DNA sequences from which they stimulate transcription. Specificity may be increased by slowing down the kinetics of regulation: by increasing the ... ...

    Abstract Specificity in transcriptional regulation is imparted by transcriptional activators that bind to specific DNA sequences from which they stimulate transcription. Specificity may be increased by slowing down the kinetics of regulation: by increasing the energy for dissociation of the activator-DNA complex or decreasing activator concentration. In general, higher dissociation energies imply longer DNA dwell times of the activator; the activator-bound gene may not readily turn off again. Lower activator concentrations entail longer pauses between binding events; the activator-unbound gene is not easily turned on again and activated transcription occurs in stochastic bursts. We show that kinetic proofreading of activator-DNA recognition-insertion of an energy-dissipating delay step into the activation pathway for transcription-reconciles high specificity of transcriptional regulation with fast regulatory kinetics. We show that kinetic proofreading results from the stochastic removal and reformation of promoter nucleosomes, at a distance from equilibrium.
    MeSH term(s) DNA/metabolism ; Gene Expression Regulation, Fungal ; Kinetics ; Nucleosomes/metabolism ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Stochastic Processes ; Trans-Activators/metabolism ; Transcription Initiation, Genetic ; Transcriptional Activation
    Chemical Substances Nucleosomes ; RNA, Messenger ; Saccharomyces cerevisiae Proteins ; Trans-Activators ; DNA (9007-49-2)
    Language English
    Publishing date 2020-01-21
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1911188117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nucleosomes, transcription, and probability.

    Boeger, Hinrich

    Molecular biology of the cell

    2014  Volume 25, Issue 22, Page(s) 3451–3455

    Abstract: Speaking of current measurements on single ion channel molecules, David Colquhoun wrote in 2006, "Individual molecules behave randomly, so suddenly we had to learn how to deal with stochastic processes." Here I describe theoretical efforts to understand ... ...

    Abstract Speaking of current measurements on single ion channel molecules, David Colquhoun wrote in 2006, "Individual molecules behave randomly, so suddenly we had to learn how to deal with stochastic processes." Here I describe theoretical efforts to understand recent experimental observations on the chromatin structure of single gene molecules, a molecular biologist's path toward probabilistic theories.
    MeSH term(s) Acid Phosphatase/genetics ; Acid Phosphatase/metabolism ; Animals ; Computer Simulation ; Markov Chains ; Models, Biological ; Models, Statistical ; Nucleosomes/chemistry ; Nucleosomes/metabolism ; Promoter Regions, Genetic ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription, Genetic
    Chemical Substances Nucleosomes ; Saccharomyces cerevisiae Proteins ; Acid Phosphatase (EC 3.1.3.2) ; PHO5 protein, S cerevisiae (EC 3.1.3.2)
    Language English
    Publishing date 2014-11-05
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E14-02-0753
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  4. Article: Probing chromatin accessibility with small molecule DNA intercalation and nanopore sequencing.

    Bai, Gali / Dhillon, Namrita / Felton, Colette / Meissner, Brett / Saint-John, Brandon / Shelansky, Robert / Meyerson, Elliot / Hrabeta-Robinson, Eva / Hodjat, Babak / Boeger, Hinrich / Brooks, Angela N

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Genome-wide identification of chromatin organization and structure has been generally probed by measuring accessibility of the underlying DNA to nucleases or methyltransferases. These methods either only observe the positioning of a single nucleosome or ... ...

    Abstract Genome-wide identification of chromatin organization and structure has been generally probed by measuring accessibility of the underlying DNA to nucleases or methyltransferases. These methods either only observe the positioning of a single nucleosome or rely on large enzymes to modify or cleave the DNA. We developed adduct sequencing (Add-seq), a method to probe chromatin accessibility by treating chromatin with the small molecule angelicin, which preferentially intercalates into DNA not bound to core nucleosomes. We show that Nanopore sequencing of the angelicin-modified DNA is possible and allows visualization and analysis of long single molecules with distinct chromatin structure. The angelicin modification can be detected from the Nanopore current signal data using a neural network model trained on unmodified and modified chromatin-free DNA. Applying Add-seq to
    Language English
    Publishing date 2024-03-22
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.20.585815
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Permutational analysis of

    Dhillon, Namrita / Shelansky, Robert / Townshend, Brent / Jain, Miten / Boeger, Hinrich / Endy, Drew / Kamakaka, Rohinton

    Synthetic biology (Oxford, England)

    2020  Volume 5, Issue 1, Page(s) ysaa007

    Abstract: Gene expression ... ...

    Abstract Gene expression in
    Language English
    Publishing date 2020-06-16
    Publishing country England
    Document type Journal Article
    ISSN 2397-7000
    ISSN (online) 2397-7000
    DOI 10.1093/synbio/ysaa007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Nucleosomal promoter variation generates gene expression noise.

    Brown, Christopher R / Boeger, Hinrich

    Proceedings of the National Academy of Sciences of the United States of America

    2014  Volume 111, Issue 50, Page(s) 17893–17898

    Abstract: Gene product molecule numbers fluctuate over time and between cells, confounding deterministic expectations. The molecular origins of this noise of gene expression remain unknown. Recent EM analysis of single PHO5 gene molecules of yeast indicated that ... ...

    Abstract Gene product molecule numbers fluctuate over time and between cells, confounding deterministic expectations. The molecular origins of this noise of gene expression remain unknown. Recent EM analysis of single PHO5 gene molecules of yeast indicated that promoter molecules stochastically assume alternative nucleosome configurations at steady state, including the fully nucleosomal and nucleosome-free configuration. Given that distinct configurations are unequally conducive to transcription, the nucleosomal variation of promoter molecules may constitute a source of gene expression noise. This notion, however, implies an untested conjecture, namely that the nucleosomal variation arises de novo or intrinsically (i.e., that it cannot be explained as the result of the promoter's deterministic response to variation in its molecular surroundings). Here, we show--by microscopically analyzing the nucleosome configurations of two juxtaposed physically linked PHO5 promoter copies--that the configurational variation, indeed, is intrinsically stochastic and thus, a cause of gene expression noise rather than its effect.
    MeSH term(s) Acid Phosphatase/genetics ; Gene Expression Regulation, Fungal/genetics ; Genetic Variation ; Microscopy, Electron ; Models, Biological ; Nucleic Acid Conformation ; Nucleosomes/genetics ; Nucleosomes/ultrastructure ; Promoter Regions, Genetic/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Stochastic Processes
    Chemical Substances Nucleosomes ; Saccharomyces cerevisiae Proteins ; Acid Phosphatase (EC 3.1.3.2) ; PHO5 protein, S cerevisiae (EC 3.1.3.2)
    Language English
    Publishing date 2014-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1417527111
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The TAFs of TFIID Bind and Rearrange the Topology of the TATA-Less

    Le, Sarah N / Brown, Christopher R / Harvey, Stacy / Boeger, Hinrich / Elmlund, Hans / Elmlund, Dominika

    International journal of molecular sciences

    2019  Volume 20, Issue 13

    Abstract: The general transcription factor TFIID is a core promoter selectivity factor that recognizes DNA sequence elements and nucleates the assembly of a pre-initiation complex (PIC). The mechanism by which TFIID recognizes the promoter is poorly understood. ... ...

    Abstract The general transcription factor TFIID is a core promoter selectivity factor that recognizes DNA sequence elements and nucleates the assembly of a pre-initiation complex (PIC). The mechanism by which TFIID recognizes the promoter is poorly understood. The TATA-box binding protein (TBP) is a subunit of the multi-protein TFIID complex believed to be key in this process. We reconstituted transcription from highly purified components on a ribosomal protein gene (
    MeSH term(s) DNA/metabolism ; Gene Rearrangement/genetics ; Genes, Essential ; Imaging, Three-Dimensional ; Promoter Regions, Genetic ; Protein Binding ; Ribosomal Proteins/genetics ; TATA Box/genetics ; TATA-Binding Protein Associated Factors/metabolism ; Transcription Factor TFIID/metabolism ; Transcription, Genetic
    Chemical Substances Ribosomal Proteins ; TATA-Binding Protein Associated Factors ; Transcription Factor TFIID ; ribosomal protein S5 ; DNA (9007-49-2)
    Language English
    Publishing date 2019-07-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20133290
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  8. Article ; Online: The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes

    Anushweta Asthana / Parameshwaran Ramanan / Alexander Hirschi / Keelan Z. Guiley / Tilini U. Wijeratne / Robert Shelansky / Michael J. Doody / Haritha Narasimhan / Hinrich Boeger / Sarvind Tripathi / Gerd A. Müller / Seth M. Rubin

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start ... ...

    Abstract The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.
    Keywords Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes.

    Asthana, Anushweta / Ramanan, Parameshwaran / Hirschi, Alexander / Guiley, Keelan Z / Wijeratne, Tilini U / Shelansky, Robert / Doody, Michael J / Narasimhan, Haritha / Boeger, Hinrich / Tripathi, Sarvind / Müller, Gerd A / Rubin, Seth M

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 526

    Abstract: The chromatin architecture in promoters is thought to regulate gene expression, but it remains uncertain how most transcription factors (TFs) impact nucleosome position. The MuvB TF complex regulates cell-cycle dependent gene-expression and is critical ... ...

    Abstract The chromatin architecture in promoters is thought to regulate gene expression, but it remains uncertain how most transcription factors (TFs) impact nucleosome position. The MuvB TF complex regulates cell-cycle dependent gene-expression and is critical for differentiation and proliferation during development and cancer. MuvB can both positively and negatively regulate expression, but the structure of MuvB and its biochemical function are poorly understood. Here we determine the overall architecture of MuvB assembly and the crystal structure of a subcomplex critical for MuvB function in gene repression. We find that the MuvB subunits LIN9 and LIN37 function as scaffolding proteins that arrange the other subunits LIN52, LIN54 and RBAP48 for TF, DNA, and histone binding, respectively. Biochemical and structural data demonstrate that MuvB binds nucleosomes through an interface that is distinct from LIN54-DNA consensus site recognition and that MuvB increases nucleosome occupancy in a reconstituted promoter. We find in arrested cells that MuvB primarily associates with a tightly positioned +1 nucleosome near the transcription start site (TSS) of MuvB-regulated genes. These results support a model that MuvB binds and stabilizes nucleosomes just downstream of the TSS on its target promoters to repress gene expression.
    MeSH term(s) Cell Cycle/genetics ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Division/physiology ; Chromatin ; DNA/metabolism ; Genes, cdc ; Nucleosomes/metabolism ; Promoter Regions, Genetic ; Protein Binding ; Transcription Factors/metabolism ; Transcription Initiation Site
    Chemical Substances Cell Cycle Proteins ; Chromatin ; Nucleosomes ; Transcription Factors ; DNA (9007-49-2)
    Language English
    Publishing date 2022-01-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-28094-1
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  10. Article ; Online: The TAFs of TFIID Bind and Rearrange the Topology of the TATA-Less RPS5 Promoter

    Sarah N. Le / Christopher R. Brown / Stacy Harvey / Hinrich Boeger / Hans Elmlund / Dominika Elmlund

    International Journal of Molecular Sciences, Vol 20, Iss 13, p

    2019  Volume 3290

    Abstract: The general transcription factor TFIID is a core promoter selectivity factor that recognizes DNA sequence elements and nucleates the assembly of a pre-initiation complex (PIC). The mechanism by which TFIID recognizes the promoter is poorly understood. ... ...

    Abstract The general transcription factor TFIID is a core promoter selectivity factor that recognizes DNA sequence elements and nucleates the assembly of a pre-initiation complex (PIC). The mechanism by which TFIID recognizes the promoter is poorly understood. The TATA-box binding protein (TBP) is a subunit of the multi-protein TFIID complex believed to be key in this process. We reconstituted transcription from highly purified components on a ribosomal protein gene ( RPS5 ) and discovered that TFIIDΔTBP binds and rearranges the promoter DNA topology independent of TBP. TFIIDΔTBP binds ~200 bp of the promoter and changes the DNA topology to a larger extent than the nucleosome core particle. We show that TBP inhibits the DNA binding activities of TFIIDΔTBP and conclude that the complete TFIID complex may represent an auto-inhibited state. Furthermore, we show that the DNA binding activities of TFIIDΔTBP are required for assembly of a PIC poised to select the correct transcription start site (TSS).
    Keywords TBP-associated factor ; TAF complex ; DNA topology ; housekeeping gene transcription ; ribosomal protein 5 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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