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  1. Article: Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.

    Ding, Xiaoyun / Wu, Yu / Rodriguez, Victoria / Ricco, Emily / Okoh, James T / Liu, Yanhong / Kraushaar, Daniel C / Rasband, Matthew N

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The bipolar disorder (BD) risk ... ...

    Abstract The bipolar disorder (BD) risk gene
    Language English
    Publishing date 2024-04-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.01.587609
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Elevating the Educational Mission of "Full-Service" Core Facilities through Formal Biotechnology Workshops.

    Ricco, Emily / Nguyen, Stacy / Rodriguez, Victoria / Pham, Kieu / Tokcan, Esmanur / Love, Sherita / Newell, Alana / Kraushaar, Daniel C

    Journal of biomolecular techniques : JBT

    2023  Volume 34, Issue 4

    Abstract: Core facility laboratories are an essential part of the successful research enterprise of many universities around the world. Core facilities provide state-of-the-art instrumentation and technologies to support research of all faculty, postdocs, and ... ...

    Abstract Core facility laboratories are an essential part of the successful research enterprise of many universities around the world. Core facilities provide state-of-the-art instrumentation and technologies to support research of all faculty, postdocs, and students on a fee-for-service basis. Academic next-generation sequencing cores are typically "full service" facilities, and access to and training on their instrumentation is limited to core staff. To address these limitations, we provided graduate students with technical training at our core facility. We developed a 1-week noncredit-bearing workshop and recruited 6 graduate students (N = 6) as part of a pilot program. The program involved online teaching, classroom-based teaching, and hands-on training in next-generation sequencing library preparation and sequencer operation. A post-participation survey revealed highly positive outcomes in terms of skill development and increased awareness of technologies offered by the core facility. A workshop of this scale could be incorporated into the graduate curriculum and extended to core facilities that focus on other technologies. We believe that introducing formal standardized teaching spearheaded by core facilities would improve the graduate student curriculum and hope that this study can provide guidance on curriculum design for similar workshops.
    MeSH term(s) Humans ; Educational Status ; Students ; Biotechnology ; Curriculum ; Faculty
    Language English
    Publishing date 2023-12-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2116011-9
    ISSN 1943-4731 ; 1943-4731
    ISSN (online) 1943-4731
    ISSN 1943-4731
    DOI 10.7171/3fc1f5fe.30644720
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Heparan sulfate is required for embryonic stem cells to exit from self-renewal.

    Kraushaar, Daniel C / Yamaguchi, Yu / Wang, Lianchun

    The Journal of biological chemistry

    2015  Volume 290, Issue 38, Page(s) 23023

    Language English
    Publishing date 2015-09-18
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.A109.066837
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The epigenomics of embryonic stem cell differentiation.

    Kraushaar, Daniel C / Zhao, Keji

    International journal of biological sciences

    2013  Volume 9, Issue 10, Page(s) 1134–1144

    Abstract: Embryonic stem cells (ESCs) possess an open and highly dynamic chromatin landscape, which underlies their plasticity and ultimately maintains ESC pluripotency. The ESC epigenome must not only maintain the transcription of pluripotency-associated genes ... ...

    Abstract Embryonic stem cells (ESCs) possess an open and highly dynamic chromatin landscape, which underlies their plasticity and ultimately maintains ESC pluripotency. The ESC epigenome must not only maintain the transcription of pluripotency-associated genes but must also, through gene priming, facilitate rapid and cell type-specific activation of developmental genes upon lineage commitment. Trans-generational inheritance ensures that the ESC chromatin state is stably transmitted from one generation to the next; yet at the same time, epigenetic marks are highly dynamic, reversible and responsive to extracellular cues. Once committed to differentiation, the ESC epigenome is remodeled and resolves into a more compact chromatin state. A thorough understanding of the role of chromatin modifiers in ESC fate and differentiation will be important if they are to be used for therapeutic purposes. Recent technical advances, particularly in next-generation sequencing technologies, have provided a genome-scale view of epigenetic marks and chromatin modifiers. More affordable and faster sequencing platforms have led to a comprehensive characterization of the ESC epigenome and epigenomes of differentiated cell types. In this review, we summarize and discuss the recent progress that has highlighted the central role of histone modifications, histone variants, DNA methylation and chromatin modifiers in ESC pluripotency and ESC fate. We provide a detailed and comprehensive discussion of genome-wide studies that are pertinent to our understanding of mammalian development.
    MeSH term(s) Adenosine Triphosphate/metabolism ; Cell Differentiation ; Chromatin Assembly and Disassembly ; DNA Methylation ; Embryonic Stem Cells/cytology ; Epigenomics ; Humans
    Chemical Substances Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2013-12-09
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 2179208-2
    ISSN 1449-2288 ; 1449-2288
    ISSN (online) 1449-2288
    ISSN 1449-2288
    DOI 10.7150/ijbs.7998
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  5. Article ; Online: The gene repressor complex NuRD interacts with the histone variant H3.3 at promoters of active genes.

    Kraushaar, Daniel C / Chen, Zuozhou / Tang, Qingsong / Cui, Kairong / Zhang, Junfang / Zhao, Keji

    Genome research

    2018  Volume 28, Issue 11, Page(s) 1646–1655

    Abstract: The histone variant H3.3 is deposited across active genes, regulatory regions, and telomeres. It remains unclear how H3.3 interacts with chromatin modifying enzymes and thereby modulates gene activity. In this study, we performed a co-immunoprecipitation- ...

    Abstract The histone variant H3.3 is deposited across active genes, regulatory regions, and telomeres. It remains unclear how H3.3 interacts with chromatin modifying enzymes and thereby modulates gene activity. In this study, we performed a co-immunoprecipitation-mass spectrometry analysis of proteins associated with H3.3-containing nucleosomes and identified the nucleosome remodeling and deacetylase complex (NuRD) as a major H3.3-interactor. We show that the H3.3-NuRD interaction is dependent on the H3.3 lysine 4 residue and that NuRD binding occurs when lysine 4 is in its unmodified state. The majority of NuRD binding colocalizes with H3.3 and directly correlates with gene activity. H3.3 depletion led to reduced levels of NuRD at sites previously occupied by H3.3, as well as a global decrease in histone marks associated with gene activation. Our results demonstrate the importance of H3.3 in the maintenance of the cellular epigenetic landscape and reveal a highly prevalent interaction between the histone variant H3.3 and the multiprotein complex NuRD.
    MeSH term(s) 3T3 Cells ; Animals ; Binding Sites ; Epigenesis, Genetic ; Histone Code ; Histones/chemistry ; Histones/genetics ; Histones/metabolism ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism ; Mice ; Protein Binding
    Chemical Substances Histones ; Mi-2 Nucleosome Remodeling and Deacetylase Complex (EC 3.5.1.98)
    Language English
    Publishing date 2018-09-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.236224.118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Genome-wide analysis of H3.3 dissociation reveals high nucleosome turnover at distal regulatory regions of embryonic stem cells.

    Ha, Misook / Kraushaar, Daniel C / Zhao, Keji

    Epigenetics & chromatin

    2014  Volume 7, Issue 1, Page(s) 38

    Abstract: Background: The histone variant H3.3 plays a critical role in maintaining the pluripotency of embryonic stem cells (ESCs) by regulating gene expression programs important for lineage specification. H3.3 is deposited by various chaperones at regulatory ... ...

    Abstract Background: The histone variant H3.3 plays a critical role in maintaining the pluripotency of embryonic stem cells (ESCs) by regulating gene expression programs important for lineage specification. H3.3 is deposited by various chaperones at regulatory sites, gene bodies, and certain heterochromatic sites such as telomeres and centromeres. Using Tet-inhibited expression of epitope-tagged H3.3 combined with ChIP-Seq we undertook genome-wide measurements of H3.3 dissociation rates across the ESC genome and examined the relationship between H3.3-nucleosome turnover and ESC-specific transcription factors, chromatin modifiers, and epigenetic marks.
    Results: Our comprehensive analysis of H3.3 dissociation rates revealed distinct H3.3 dissociation dynamics at various functional chromatin domains. At transcription start sites, H3.3 dissociates rapidly with the highest rate at nucleosome-depleted regions (NDRs) just upstream of Pol II binding, followed by low H3.3 dissociation rates across gene bodies. H3.3 turnover at transcription start sites, gene bodies, and transcription end sites was positively correlated with transcriptional activity. H3.3 is found decorated with various histone modifications that regulate transcription and maintain chromatin integrity. We find greatly varying H3.3 dissociation rates across various histone modification domains: high dissociation rates at active histone marks and low dissociation rates at heterochromatic marks. Well- defined zones of high H3.3-nucleosome turnover were detected at binding sites of ESC-specific pluripotency factors and chromatin remodelers, suggesting an important role for H3.3 in facilitating protein binding. Among transcription factor binding sites we detected higher H3.3 turnover at distal cis-acting sites compared to proximal genic transcription factor binding sites. Our results imply that fast H3.3 dissociation is a hallmark of interactions between DNA and transcriptional regulators.
    Conclusion: Our study demonstrates that H3.3 turnover and nucleosome stability vary greatly across the chromatin landscape of embryonic stem cells. The presence of high H3.3 turnover at RNA Pol II binding sites at extragenic regions as well as at transcription start and end sites of genes, suggests a specific role for H3.3 in transcriptional initiation and termination. On the other hand, the presence of well-defined zones of high H3.3 dissociation at transcription factor and chromatin remodeler binding sites point to a broader role in facilitating accessibility.
    Language English
    Publishing date 2014
    Publishing country England
    Document type Journal Article
    ZDB-ID 2462129-8
    ISSN 1756-8935
    ISSN 1756-8935
    DOI 10.1186/1756-8935-7-38
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  7. Article ; Online: Erratum to: Genome-wide incorporation dynamics reveal distinct categories of turnover for the histone variant H3.3.

    Kraushaar, Daniel C / Jin, Wenfei / Maunakea, Alika / Abraham, Brian / Ha, Misook / Zhao, Keji

    Genome biology

    2016  Volume 17, Page(s) 21

    Language English
    Publishing date 2016-02-04
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/s13059-016-0886-3
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  8. Article ; Online: Heparan sulfate: a key regulator of embryonic stem cell fate.

    Kraushaar, Daniel C / Dalton, Stephen / Wang, Lianchun

    Biological chemistry

    2013  Volume 394, Issue 6, Page(s) 741–751

    Abstract: Heparan sulfate (HS) belongs to a class of glycosaminoglycans and is a highly sulfated, linear polysaccharide. HS biosynthesis and modification involves numerous enzymes. HS exists as part of glycoproteins named HS proteoglycans, which are expressed ... ...

    Abstract Heparan sulfate (HS) belongs to a class of glycosaminoglycans and is a highly sulfated, linear polysaccharide. HS biosynthesis and modification involves numerous enzymes. HS exists as part of glycoproteins named HS proteoglycans, which are expressed abundantly on the cell surface and in the extracellular matrix. HS interacts with numerous proteins, including growth factors, morphogens, and adhesion molecules, and thereby regulates important developmental processes in invertebrates and vertebrates. Embryonic stem cells (ESCs) are distinguished by their characteristics of self-renewal and pluripotency. Self-renewal allows ESCs to proliferate indefinitely in their undifferentiated state, whereas pluripotency implies their capacity to differentiate into the three germ layers and ultimately all cell types of the adult body. Both traits are tightly regulated by numerous cell signaling pathways. Recent studies have highlighted the importance of HS in the modulation of ESC functions, specifically their lineage fate. Here, we review the current advances that have been made in understanding the structural changes of HS during ESC differentiation and in deciphering the molecular mechanisms by which HS modulates cell fate. Finally, we discuss the applications of heparinoids and chemical inhibitors of HS biosynthesis for the manipulation of ESC culture and directed differentiation.
    MeSH term(s) Animals ; Cell Culture Techniques ; Cell Lineage/drug effects ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/drug effects ; Embryonic Stem Cells/metabolism ; Heparinoids/pharmacology ; Heparitin Sulfate/biosynthesis ; Heparitin Sulfate/chemistry ; Heparitin Sulfate/metabolism ; Humans ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/drug effects ; Pluripotent Stem Cells/metabolism
    Chemical Substances Heparinoids ; Heparitin Sulfate (9050-30-0)
    Language English
    Publishing date 2013-02-01
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2012-0353
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  9. Article ; Online: Transcriptome, proteome, and protein synthesis within the intracellular cytomatrix.

    Shaiken, Tattym E / Grimm, Sandra L / Siam, Mohamad / Williams, Amanda / Rezaeian, Abdol-Hossein / Kraushaar, Daniel / Ricco, Emily / Robertson, Matthew J / Coarfa, Cristian / Jain, Antrix / Malovannaya, Anna / Stossi, Fabio / Opekun, Antone R / Price, Alyssa P / Dubrulle, Julien

    iScience

    2023  Volume 26, Issue 2, Page(s) 105965

    Abstract: Despite the knowledge that protein translation and various metabolic reactions that create and sustain cellular life occur in the cytoplasm, the structural organization within the cytoplasm remains unclear. Recent models indicate that cytoplasm contains ... ...

    Abstract Despite the knowledge that protein translation and various metabolic reactions that create and sustain cellular life occur in the cytoplasm, the structural organization within the cytoplasm remains unclear. Recent models indicate that cytoplasm contains viscous fluid and elastic solid phases. We separated these viscous fluid and solid elastic compartments, which we call the cytosol and cytomatrix, respectively. The distinctive composition of the cytomatrix included structural proteins, ribosomes, and metabolome enzymes. High-throughput analysis revealed unique biosynthetic pathways within the cytomatrix. Enrichment of biosynthetic pathways in the cytomatrix indicated the presence of immobilized biocatalysis. Enzymatic immobilization and segregation can surmount spatial impediments, and the local pathway segregation may form cytoplasmic organelles. Protein translation was reprogrammed within the cytomatrix under the restriction of protein synthesis by drug treatment. The cytosol and cytomatrix are an elaborately interconnected network that promotes operational flexibility in healthy cells and the survival of malignant cells.
    Language English
    Publishing date 2023-01-13
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.105965
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  10. Article ; Online: Exogenous inter-α inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice.

    McCullough, Louise D / Roy-O'Reilly, Meaghan / Lai, Yun-Ju / Patrizz, Anthony / Xu, Yan / Lee, Juneyoung / Holmes, Aleah / Kraushaar, Daniel C / Chauhan, Anjali / Sansing, Lauren H / Stonestreet, Barbara S / Zhu, Liang / Kofler, Julia / Lim, Yow-Pin / Venna, Venugopal Reddy

    The Journal of clinical investigation

    2021  Volume 131, Issue 17

    Abstract: Inter-α inhibitor proteins (IAIPs) are a family of endogenous plasma and extracellular matrix molecules. IAIPs suppress proinflammatory cytokines, limit excess complement activation, and bind extracellular histones to form IAIP-histone complexes, leading ...

    Abstract Inter-α inhibitor proteins (IAIPs) are a family of endogenous plasma and extracellular matrix molecules. IAIPs suppress proinflammatory cytokines, limit excess complement activation, and bind extracellular histones to form IAIP-histone complexes, leading to neutralization of histone-associated cytotoxicity in models of sepsis. Many of these detrimental processes also play critical roles in the pathophysiology of ischemic stroke. In this study, we first assessed the clinical relevance of IAIPs in stroke and then tested the therapeutic efficacy of exogenous IAIPs in several experimental stroke models. IAIP levels were reduced in both ischemic stroke patients and in mice subjected to experimental ischemic stroke when compared with controls. Post-stroke administration of IAIP significantly improved stroke outcomes across multiple stroke models, even when given 6 hours after stroke onset. Importantly, the beneficial effects of delayed IAIP treatment were observed in both young and aged mice. Using targeted gene expression analysis, we identified a receptor for complement activation, C5aR1, that was highly suppressed in both the blood and brain of IAIP-treated animals. Subsequent experiments using C5aR1-knockout mice demonstrated that the beneficial effects of IAIPs are mediated in part by C5aR1. These results indicate that IAIP is a potential therapeutic candidate for the treatment of ischemic stroke.
    MeSH term(s) Alpha-Globulins/administration & dosage ; Alpha-Globulins/metabolism ; Alpha-Globulins/therapeutic use ; Animals ; Brain Edema/drug therapy ; Brain Edema/pathology ; Brain Infarction/drug therapy ; Brain Infarction/pathology ; Cell Death/drug effects ; Disease Models, Animal ; Female ; Humans ; Ischemic Stroke/drug therapy ; Ischemic Stroke/metabolism ; Ischemic Stroke/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor, Anaphylatoxin C5a/deficiency ; Receptor, Anaphylatoxin C5a/genetics ; Receptor, Anaphylatoxin C5a/metabolism ; Tissue Plasminogen Activator/administration & dosage
    Chemical Substances Alpha-Globulins ; C5ar1 protein, mouse ; Receptor, Anaphylatoxin C5a ; inter-alpha-inhibitor (39346-44-6) ; Tissue Plasminogen Activator (EC 3.4.21.68)
    Language English
    Publishing date 2021-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI144898
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