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  1. Article: Understanding how genetically encoded tags affect phase separation by Heterochromatin Protein HP1α.

    Zhou, Ziling Kate / Narlikar, Geeta J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Liquid-liquid phase separation (LLPS) is driven by weak multi-valent interactions. Such interactions can result in the formation of puncta in cells and ... ...

    Abstract Liquid-liquid phase separation (LLPS) is driven by weak multi-valent interactions. Such interactions can result in the formation of puncta in cells and droplets
    Language English
    Publishing date 2023-12-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.04.569983
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hexasomal particles: consequence or also consequential?

    Kaur, Upneet / Muñoz, Elise N / Narlikar, Geeta J

    Current opinion in genetics & development

    2024  Volume 85, Page(s) 102163

    Abstract: It is long known that an RNA polymerase transcribing through a nucleosome can generate subnucleosomal particles called hexasomes. These particles lack an H2A-H2B dimer, breaking the symmetry of a nucleosome and revealing new interfaces. Whether hexasomes ...

    Abstract It is long known that an RNA polymerase transcribing through a nucleosome can generate subnucleosomal particles called hexasomes. These particles lack an H2A-H2B dimer, breaking the symmetry of a nucleosome and revealing new interfaces. Whether hexasomes are simply a consequence of RNA polymerase action or they also have a regulatory impact remains an open question. Recent biochemical and structural studies of RNA polymerases and chromatin remodelers with hexasomes motivated us to revisit this question. Here, we build on previous models to discuss how formation of hexasomes can allow sophisticated regulation of transcription and also significantly impact chromatin folding. We anticipate that further cellular and biochemical analysis of these subnucleosomal particles will uncover additional regulatory roles.
    MeSH term(s) Nucleosomes/genetics ; Chromatin/genetics ; DNA-Directed RNA Polymerases/genetics
    Chemical Substances Nucleosomes ; Chromatin ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
    Language English
    Publishing date 2024-02-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2024.102163
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Phase-separation in chromatin organization.

    Narlikar, Geeta J

    Journal of biosciences

    2020  Volume 45

    Abstract: The organization of chromatin into different types of compact versus open states provides a means to fine tune gene regulation. Recent studies have suggested a role for phase-separation in chromatin compaction, raising new possibilities for regulating ... ...

    Abstract The organization of chromatin into different types of compact versus open states provides a means to fine tune gene regulation. Recent studies have suggested a role for phase-separation in chromatin compaction, raising new possibilities for regulating chromatin compartments. This perspective discusses some specific molecular mechanisms that could leverage such phase-separation processes to control the functions and organization of chromatin.
    MeSH term(s) Chromatin/genetics ; Chromatin/ultrastructure ; Gene Expression Regulation/genetics ; Heterochromatin/genetics ; Heterochromatin/ultrastructure ; Histones/genetics ; Nucleosomes/genetics
    Chemical Substances Chromatin ; Heterochromatin ; Histones ; Nucleosomes
    Language English
    Publishing date 2020-01-18
    Publishing country India
    Document type Journal Article
    ZDB-ID 756157-x
    ISSN 0973-7138 ; 0250-5991
    ISSN (online) 0973-7138
    ISSN 0250-5991
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: ATP Hydrolysis Coordinates the Activities of Two Motors in a Dimeric Chromatin Remodeling Enzyme.

    Johnson, Stephanie L / Narlikar, Geeta J

    Journal of molecular biology

    2022  Volume 434, Issue 14, Page(s) 167653

    Abstract: ATP-dependent chromatin remodelers are essential enzymes that restructure eukaryotic genomes to enable all DNA-based processes. The diversity and complexity of these processes arethe complexity of the enzymes that carry them out, making remodelers a ... ...

    Abstract ATP-dependent chromatin remodelers are essential enzymes that restructure eukaryotic genomes to enable all DNA-based processes. The diversity and complexity of these processes arethe complexity of the enzymes that carry them out, making remodelers a challenging class of molecular motors to study by conventional methods. Here we use a single molecule biophysical assay to overcome some of these challenges, enabling a detailed mechanistic dissection of a paradigmatic remodeler reaction, that of sliding a nucleosome towards the longer DNA linker. We focus on how two motors of a dimeric remodeler coordinate to accomplish such directional sliding. We find that ATP hydrolysis by both motors promotes coordination, suggesting a role for ATP in resolving the competition for directional commitment. Furthermore, we show an artificially constitutive dimer is no more or less coordinated, but is more processive, suggesting a cell could modulate a remodeler's oligomeric state to modulate local chromatin dynamics.
    MeSH term(s) Adenosine Triphosphate ; Chromatin ; Chromatin Assembly and Disassembly ; DNA ; Hydrolysis ; Nucleosomes
    Chemical Substances Chromatin ; Nucleosomes ; Adenosine Triphosphate (8L70Q75FXE) ; DNA (9007-49-2)
    Language English
    Publishing date 2022-06-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2022.167653
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Histone dynamics play a critical role in SNF2h-mediated nucleosome sliding.

    Gamarra, Nathan / Narlikar, Geeta J

    Nature structural & molecular biology

    2021  Volume 28, Issue 7, Page(s) 548–551

    MeSH term(s) Chromatin Assembly and Disassembly ; Histones/metabolism ; Nucleosomes
    Chemical Substances Histones ; Nucleosomes
    Language English
    Publishing date 2021-07-05
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-021-00620-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Collaboration through chromatin: motors of transcription and chromatin structure.

    Gamarra, Nathan / Narlikar, Geeta J

    Journal of molecular biology

    2021  Volume 433, Issue 14, Page(s) 166876

    Abstract: Packaging of the eukaryotic genome into chromatin places fundamental physical constraints on transcription. Clarifying how transcription operates within these constraints is essential to understand how eukaryotic gene expression programs are established ... ...

    Abstract Packaging of the eukaryotic genome into chromatin places fundamental physical constraints on transcription. Clarifying how transcription operates within these constraints is essential to understand how eukaryotic gene expression programs are established and maintained. Here we review what is known about the mechanisms of transcription on chromatin templates. Current models indicate that transcription through chromatin is accomplished by the combination of an inherent nucleosome disrupting activity of RNA polymerase and the action of ATP-dependent chromatin remodeling motors. Collaboration between these two types of molecular motors is proposed to occur at all stages of transcription through diverse mechanisms. Further investigation of how these two motors combine their basic activities is essential to clarify the interdependent relationship between genome structure and transcription.
    MeSH term(s) Adenosine Triphosphatases/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; DNA-Directed RNA Polymerases/metabolism ; Gene Expression Regulation ; Nucleosomes/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; Nucleosomes ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Adenosine Triphosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2021-02-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2021.166876
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Generation and Biochemical Characterization of Phase-Separated Droplets Formed by Nucleic Acid Binding Proteins: Using HP1 as a Model System.

    Sanulli, Serena / Narlikar, Geeta J

    Current protocols

    2021  Volume 1, Issue 5, Page(s) e109

    Abstract: Liquid-liquid phase separation (LLPS) has been invoked as an underlying mechanism involved in the formation and function of several cellular membrane-less compartments. Given the explosion of studies in this field in recent years, it has become essential ...

    Abstract Liquid-liquid phase separation (LLPS) has been invoked as an underlying mechanism involved in the formation and function of several cellular membrane-less compartments. Given the explosion of studies in this field in recent years, it has become essential to converge on clear guidelines and methods to rigorously investigate LLPS and advance our understanding of this phenomenon. Here, we describe basic methods to (1) visualize droplets formed by nucleic acid binding proteins and (2) characterize the liquid-like nature of these droplets under controlled in vitro experimental conditions. We discuss the rationale behind these methods, as well as caveats and limitations. Our ultimate goal is to guide scientists interested in learning how to test for LLPS, while appreciating that the field is evolving rapidly and adjusting constantly to the growing knowledge. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Observing phase-separated condensates by microscopy. Support Protocol: Coating of glass-bottom plates. Basic Protocol 2: Assessing condensate reversibility by changing ionic strength. Alternate Protocol 1: Assessing condensate reversibility by dilution. Alternate Protocol 2: Assessing condensate reversibility by altering temperature. Basic Protocol 3: Quantifying phase separation by centrifugation assay. Basic Protocol 4: Quantifying phase separation by turbidity assay.
    MeSH term(s) Carrier Proteins ; Centrifugation ; Chromosomal Proteins, Non-Histone ; Nucleic Acids ; Osmolar Concentration
    Chemical Substances Carrier Proteins ; Chromosomal Proteins, Non-Histone ; Nucleic Acids
    Language English
    Publishing date 2021-04-14
    Publishing country United States
    Document type Journal Article
    ISSN 2691-1299
    ISSN (online) 2691-1299
    DOI 10.1002/cpz1.109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Liquid-like interactions in heterochromatin: Implications for mechanism and regulation.

    Sanulli, Serena / J Narlikar, Geeta

    Current opinion in cell biology

    2020  Volume 64, Page(s) 90–96

    Abstract: A large portion of the eukaryotic genome is packed into heterochromatin, a versatile platform that is essential to maintain genome stability. Often associated with a compact and transcriptionally repressed chromatin state, heterochromatin was earlier ... ...

    Abstract A large portion of the eukaryotic genome is packed into heterochromatin, a versatile platform that is essential to maintain genome stability. Often associated with a compact and transcriptionally repressed chromatin state, heterochromatin was earlier considered a static and locked compartment. However, cumulative findings over the last 17 years have suggested that heterochromatin displays dynamics at different timescales and size scales. These dynamics are thought to be essential for the regulation of heterochromatin. This review illustrates how the key principles underlying heterochromatin structure and function have evolved along the years and summarizes the discoveries that have led to the continuous revision of these principles. Using heterochromatin protein 1-mediated heterochromatin as a context, we discuss a novel paradigm for heterochromatin organization based on two emerging concepts, phase separation and nucleosome structural plasticity. We also examine the broader implications of this paradigm for chromatin organization and regulation beyond heterochromatin.
    MeSH term(s) Chromosomal Proteins, Non-Histone/metabolism ; Genomic Instability ; Heterochromatin/metabolism ; Humans ; Models, Biological ; Nucleosomes/metabolism
    Chemical Substances Chromosomal Proteins, Non-Histone ; Heterochromatin ; Nucleosomes ; heterochromatin-specific nonhistone chromosomal protein HP-1 (107283-02-3)
    Language English
    Publishing date 2020-05-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2020.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Collaboration through chromatin: motors of transcription and chromatin structure

    Gamarra, Nathan / Narlikar, Geeta J

    Journal of molecular biology. 2021 July 09, v. 433, no. 14

    2021  

    Abstract: Packaging of the eukaryotic genome into chromatin places fundamental physical constraints on transcription. Clarifying how transcription operates within these constraints is essential to understand how eukaryotic gene expression programs are established ... ...

    Abstract Packaging of the eukaryotic genome into chromatin places fundamental physical constraints on transcription. Clarifying how transcription operates within these constraints is essential to understand how eukaryotic gene expression programs are established and maintained. Here we review what is known about the mechanisms of transcription on chromatin templates. Current models indicate that transcription through chromatin is accomplished by the combination of an inherent nucleosome disrupting activity of RNA polymerase and the action of ATP-dependent chromatin remodeling motors. Collaboration between these two types of molecular motors is proposed to occur at all stages of transcription through diverse mechanisms. Further investigation of how these two motors combine their basic activities is essential to clarify the interdependent relationship between genome structure and transcription.
    Keywords DNA-directed RNA polymerase ; gene expression ; genome ; molecular biology ; nucleosomes
    Language English
    Dates of publication 2021-0709
    Publishing place Elsevier Ltd
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2021.166876
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Reorientation of INO80 on hexasomes reveals basis for mechanistic versatility.

    Wu, Hao / Muñoz, Elise N / Hsieh, Laura J / Chio, Un Seng / Gourdet, Muryam A / Narlikar, Geeta J / Cheng, Yifan

    Science (New York, N.Y.)

    2023  Volume 381, Issue 6655, Page(s) 319–324

    Abstract: Unlike other chromatin remodelers, INO80 preferentially mobilizes hexasomes, which can form during transcription. Why INO80 prefers hexasomes over nucleosomes remains unclear. Here, we report structures ... ...

    Abstract Unlike other chromatin remodelers, INO80 preferentially mobilizes hexasomes, which can form during transcription. Why INO80 prefers hexasomes over nucleosomes remains unclear. Here, we report structures of
    MeSH term(s) Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Histones/metabolism ; Nucleosomes/chemistry ; Saccharomyces cerevisiae/chemistry ; Saccharomyces cerevisiae/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry
    Chemical Substances Chromatin ; Histones ; Nucleosomes ; Saccharomyces cerevisiae Proteins ; INO80 complex, S cerevisiae
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adf4197
    Database MEDical Literature Analysis and Retrieval System OnLINE

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