LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 20

Search options

  1. Article: A transcription factor (TF) inference method that broadly measures TF activity and identifies mechanistically distinct TF networks.

    Jones, Taylor / Sigauke, Rutendo F / Sanford, Lynn / Taatjes, Dylan J / Allen, Mary A / Dowell, Robin D

    bioRxiv : the preprint server for biology

    2024  

    Abstract: TF profiler is a method of inferring transcription factor regulatory activity, i.e. when a TF is present and actively regulating transcription, directly directly from nascent sequencing assays such as PRO-seq and GRO-seq. Transcription factors ... ...

    Abstract TF profiler is a method of inferring transcription factor regulatory activity, i.e. when a TF is present and actively regulating transcription, directly directly from nascent sequencing assays such as PRO-seq and GRO-seq. Transcription factors orchestrate transcription and play a critical role in cellular maintenance, identity and response to external stimuli. While ChIP assays have measured DNA localization, they fall short of identifying when and where transcription factors are actively regulating transcription. Our method, on the other hand, uses RNA polymerase activity to infer TF activity across hundreds of data sets and transcription factors. Based on these classifications we identify three distinct classes of transcription factors: ubiquitous factors that play roles in cellular homeostasis, driving basal gene programs across tissues and cell types, tissue specific factors that act almost exclusively at enhancers and are themselves regulated at transcription, and stimulus responsive TFs which are regulated post-transcriptionally but act predominantly at enhancers. TF profiler is broadly applicable, providing regulatory insights on any PRO-seq sample for any transcription factor with a known binding motif.
    Language English
    Publishing date 2024-03-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.15.585303
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Dissociated Hippocampal Neurons Exhibit Distinct Zn

    Sanford, Lynn / Palmer, Amy E

    ACS chemical neuroscience

    2020  Volume 11, Issue 4, Page(s) 508–514

    Abstract: ... Ionic ... ...

    Abstract Ionic Zn
    MeSH term(s) Animals ; Calcium/metabolism ; Glutamic Acid/metabolism ; Hippocampus/metabolism ; Homeostasis/drug effects ; Hydrogen-Ion Concentration ; Mice ; Neurons/metabolism ; Signal Transduction/drug effects ; Zinc/metabolism
    Chemical Substances Glutamic Acid (3KX376GY7L) ; Zinc (J41CSQ7QDS) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2020-02-06
    Publishing country United States
    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.
    ISSN 1948-7193
    ISSN (online) 1948-7193
    DOI 10.1021/acschemneuro.0c00006
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Cellular zinc status alters chromatin accessibility and binding of transcription factor p53 to genomic sites.

    Damon, Leah J / Ocampo, Daniel / Sanford, Lynn / Jones, Taylor / Allen, Mary A / Dowell, Robin D / Palmer, Amy E

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... Zinc ( ... ...

    Abstract Zinc (Zn
    Language English
    Publishing date 2023-11-21
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.20.567954
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Recent Advances in Development of Genetically Encoded Fluorescent Sensors.

    Sanford, Lynn / Palmer, Amy

    Methods in enzymology

    2017  Volume 589, Page(s) 1–49

    Abstract: Genetically encoded fluorescent sensors are essential tools in modern biological research, and recent advances in fluorescent proteins (FPs) have expanded the scope of sensor design and implementation. In this review we compare different sensor platforms, ...

    Abstract Genetically encoded fluorescent sensors are essential tools in modern biological research, and recent advances in fluorescent proteins (FPs) have expanded the scope of sensor design and implementation. In this review we compare different sensor platforms, including Förster resonance energy transfer (FRET) sensors, fluorescence-modulated single FP-based sensors, translocation sensors, complementation sensors, and dimerization-based sensors. We discuss elements of sensor design and engineering for each platform, including the incorporation of new types of FPs and sensor screening techniques. Finally, we summarize the wide range of sensors in the literature, exploring creative new sensor architectures suitable for different applications.
    MeSH term(s) Animals ; Biosensing Techniques/methods ; Fluorescence Resonance Energy Transfer/methods ; Fluorescent Dyes/analysis ; Fluorescent Dyes/metabolism ; Humans ; Luminescent Proteins/analysis ; Luminescent Proteins/genetics
    Chemical Substances Fluorescent Dyes ; Luminescent Proteins
    Language English
    Publishing date 2017-03-09
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1557-7988 ; 0076-6879
    ISSN (online) 1557-7988
    ISSN 0076-6879
    DOI 10.1016/bs.mie.2017.01.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article: Atlas of nascent RNA transcripts reveals enhancer to gene linkages.

    Sigauke, Rutendo F / Sanford, Lynn / Maas, Zachary L / Jones, Taylor / Stanley, Jacob T / Townsend, Hope A / Allen, Mary A / Dowell, Robin D

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Gene transcription is controlled and modulated by regulatory regions, including enhancers and promoters. These regions are abundant in unstable, non-coding bidirectional transcription. Using nascent RNA transcription data across hundreds of human samples, ...

    Abstract Gene transcription is controlled and modulated by regulatory regions, including enhancers and promoters. These regions are abundant in unstable, non-coding bidirectional transcription. Using nascent RNA transcription data across hundreds of human samples, we identified over 800,000 regions containing bidirectional transcription. We then identify highly correlated transcription between bidirectional and gene regions. The identified correlated pairs, a bidirectional region and a gene, are enriched for disease associated SNPs and often supported by independent 3D data. We present these resources as an SQL database which serves as a resource for future studies into gene regulation, enhancer associated RNAs, and transcription factors.
    Language English
    Publishing date 2023-12-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.07.570626
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Intracellular Zn

    Sanford, Lynn / Carpenter, Margaret C / Palmer, Amy E

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 9411

    Abstract: ... Zinc ( ... ...

    Abstract Zinc (Zn
    MeSH term(s) Animals ; Biological Transport ; Biomarkers ; Cells, Cultured ; Computational Biology/methods ; Female ; Fluorescent Antibody Technique ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Ontology ; Pyramidal Cells/metabolism ; Rats ; Signal Transduction ; Synaptic Vesicles/metabolism ; Zinc/metabolism
    Chemical Substances Biomarkers ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2019-06-28
    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 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-45844-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Deconvolution of multiplexed transcriptional responses to wood smoke particles defines rapid aryl hydrocarbon receptor signaling dynamics.

    Gupta, Arnav / Sasse, Sarah K / Gruca, Margaret A / Sanford, Lynn / Dowell, Robin D / Gerber, Anthony N

    The Journal of biological chemistry

    2021  Volume 297, Issue 4, Page(s) 101147

    Abstract: The heterogeneity of respirable particulates and compounds complicates our understanding of transcriptional responses to air pollution. Here, we address this by applying precision nuclear run-on sequencing and the assay for transposase-accessible ... ...

    Abstract The heterogeneity of respirable particulates and compounds complicates our understanding of transcriptional responses to air pollution. Here, we address this by applying precision nuclear run-on sequencing and the assay for transposase-accessible chromatin sequencing to measure nascent transcription and chromatin accessibility in airway epithelial cells after wood smoke particle (WSP) exposure. We used transcription factor enrichment analysis to identify temporally distinct roles for ternary response factor-serum response factor complexes, the aryl hydrocarbon receptor (AHR), and NFκB in regulating transcriptional changes induced by WSP. Transcription of canonical targets of the AHR, such as CYP1A1 and AHRR, was robustly increased after just 30 min of WSP exposure, and we discovered novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L. Transcription of these genes and associated enhancers rapidly returned to near baseline by 120 min after exposure. The kinetics of AHR- and NFκB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining NFκB-mediated responses through 120 min of exposure. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFκB signaling in controlling proinflammatory gene expression. This work also defines an integrated genomics-based strategy for deconvoluting multiplexed transcriptional responses to heterogeneous environmental exposures.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Line, Transformed ; Chromatin Assembly and Disassembly ; Cytochrome P-450 CYP1A1/biosynthesis ; Cytochrome P-450 CYP1A1/genetics ; DNA (Cytosine-5-)-Methyltransferases/biosynthesis ; DNA (Cytosine-5-)-Methyltransferases/genetics ; Humans ; Mice ; NF-kappa B/genetics ; NF-kappa B/metabolism ; NIH 3T3 Cells ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Signal Transduction ; Smoke/adverse effects ; Transcription, Genetic ; Wood
    Chemical Substances AHR protein, human ; AHRR protein, human ; Basic Helix-Loop-Helix Transcription Factors ; NF-kappa B ; Receptors, Aryl Hydrocarbon ; Repressor Proteins ; Smoke ; CYP1A1 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; DNMT3L protein, human (EC 2.1.1.-) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37)
    Language English
    Publishing date 2021-09-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2021.101147
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article: Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.

    Cozzolino, Kira / Sanford, Lynn / Hunter, Samuel / Molison, Kayla / Erickson, Benjamin / Jones, Taylor / Ajit, Deepa / Galbraith, Matthew D / Espinosa, Joaquin M / Bentley, David L / Allen, Mary A / Dowell, Robin D / Taatjes, Dylan J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Hyperactive interferon (IFN) signaling is a hallmark of Down syndrome (DS), a condition caused by trisomy 21 (T21); strategies that normalize IFN signaling could benefit this population. Mediator-associated kinases CDK8 and CDK19 drive inflammatory ... ...

    Abstract Hyperactive interferon (IFN) signaling is a hallmark of Down syndrome (DS), a condition caused by trisomy 21 (T21); strategies that normalize IFN signaling could benefit this population. Mediator-associated kinases CDK8 and CDK19 drive inflammatory responses through incompletely understood mechanisms. Using sibling-matched cell lines with/without T21, we investigated Mediator kinase function in the context of hyperactive IFN in DS. Activation of IFN-response genes was suppressed in cells treated with the CDK8/CDK19 inhibitor cortistatin A, and this occurred through suppression of IFN-responsive transcription factor activity. Moreover, we discovered that CDK8/CDK19 affect splicing, a novel means by which Mediator kinases control gene expression. Kinase inhibition altered splicing in pathway-specific ways and selectively affected IFN-responsive gene splicing in T21 cells. To further probe Mediator kinase function, we completed cytokine screens and untargeted metabolomics experiments. Cytokines are master regulators of inflammatory responses; by screening 105 different cytokine proteins, we show that Mediator kinases help drive IFN-dependent cytokine responses at least in part through transcriptional regulation of cytokine genes and receptors. Metabolomics revealed that Mediator kinase inhibition altered core metabolic pathways, including broad up-regulation of anti-inflammatory lipid mediators. Elevated levels of lipid mediators persisted at least 24hr after Mediator kinase inhibition, and many identified lipids serve as ligands for nuclear receptors (e.g. PPAR, LXR) or G-protein coupled receptors (GPCRs; e.g. FFAR4). Notably, ligand-dependent activation of these GPCRs or nuclear receptors will propagate anti-inflammatory signaling pathways and gene expression programs, and this mechanistic link suggests that metabolic changes caused by CDK8/CDK19 inhibition can durably and independently suppress pro-inflammatory IFN responses. Collectively, our results establish that Mediator kinase inhibition antagonizes IFN signaling through transcriptional, metabolic, and cytokine responses, with implications for DS and other chronic inflammatory conditions.
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.05.547813
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Remodeling of Zn

    Han, Yu / Sanford, Lynn / Simpson, David M / Dowell, Robin D / Palmer, Amy E

    Metallomics : integrated biometal science

    2020  Volume 12, Issue 3, Page(s) 346–362

    Abstract: Zinc is the second most abundant transition metal in humans and an essential nutrient required for growth and development of newborns. During lactation, mammary epithelial cells differentiate into a secretory phenotype, uptake zinc from blood circulation, ...

    Abstract Zinc is the second most abundant transition metal in humans and an essential nutrient required for growth and development of newborns. During lactation, mammary epithelial cells differentiate into a secretory phenotype, uptake zinc from blood circulation, and export it into mother's milk. At the cellular level, many zinc-dependent cellular processes, such as transcription, metabolism of nutrients, and proliferation are involved in the differentiation of mammary epithelial cells. Using mouse mammary epithelial cells as a model system, we investigated the remodeling of zinc homeostasis during differentiation induced by treatment with the lactogenic hormones cortisol and prolactin. RNA-Seq at different stages of differentiation revealed changes in global gene expression, including genes encoding zinc-dependent proteins and regulators of zinc homeostasis. Increases in mRNA levels of three zinc homeostasis genes, Slc39a14 (ZIP14) and metallothioneins (MTs) I and II were induced by cortisol but not by prolactin. The cortisol-induced increase was partially mediated by the nuclear glucocorticoid receptor signaling pathway. An increase in the cytosolic labile Zn2+ pool was also detected in lactating mammary cells, consistent with upregulation of MTs. We found that the zinc transporter ZIP14 was important for the expression of a major milk protein, whey acid protein (WAP), as knockdown of ZIP14 dramatically decreased WAP mRNA levels. In summary, our study demonstrated remodeling of zinc homeostasis upon differentiation of mammary epithelial cells resulting in changes in cytosolic Zn2+ and differential expression of zinc homeostasis genes, and these changes are important for establishing the lactation phenotype.
    MeSH term(s) Animals ; Cations, Divalent/metabolism ; Cell Differentiation ; Cell Line ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Gene Expression Regulation ; Homeostasis ; Hydrocortisone/metabolism ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/metabolism ; Mice ; Prolactin/metabolism ; Zinc/metabolism
    Chemical Substances Cations, Divalent ; Prolactin (9002-62-4) ; Zinc (J41CSQ7QDS) ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2020-01-09
    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 2474317-3
    ISSN 1756-591X ; 1756-5901
    ISSN (online) 1756-591X
    ISSN 1756-5901
    DOI 10.1039/c9mt00301k
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Noncoding SNPs decrease expression of FABP5 during COPD exacerbations.

    El Kharbili, Manale / Sasse, Sarah K / Sanford, Lynn / Jacobson, Sean / Aviszus, Katja / Gupta, Arnav / Guo, Claire / Majka, Susan M / Dowell, Robin D / Gerber, Anthony N / Bowler, Russell P / Gally, Fabienne

    The Journal of clinical investigation

    2023  Volume 134, Issue 3

    MeSH term(s) Humans ; Polymorphism, Single Nucleotide ; Pulmonary Disease, Chronic Obstructive/genetics ; Risk Factors ; Disease Progression ; Fatty Acid-Binding Proteins/genetics ; Fatty Acid-Binding Proteins/metabolism
    Chemical Substances FABP5 protein, human ; Fatty Acid-Binding Proteins
    Language English
    Publishing date 2023-12-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI175626
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top