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  1. Article: Working a second job: Cell adhesion proteins that moonlight in the nucleus.

    Haage, Amanda / Dhasarathy, Archana

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1163553

    Abstract: Cells are adept at sensing changes in their environment, transmitting signals internally to coordinate responses to external stimuli, and thereby influencing adaptive changes in cell states and behavior. Often, this response involves modulation of gene ... ...

    Abstract Cells are adept at sensing changes in their environment, transmitting signals internally to coordinate responses to external stimuli, and thereby influencing adaptive changes in cell states and behavior. Often, this response involves modulation of gene expression in the nucleus, which is seen largely as a physically separated process from the rest of the cell. Mechanosensing, whereby a cell senses physical stimuli, and integrates and converts these inputs into downstream responses including signaling cascades and gene regulatory changes, involves the participation of several macromolecular structures. Of note, the extracellular matrix (ECM) and its constituent macromolecules comprise an essential part of the cellular microenvironment, allowing cells to interact with each other, and providing both structural and biochemical stimuli sensed by adhesion transmembrane receptors. This highway of information between the ECM, cell adhesion proteins, and the cytoskeleton regulates cellular behavior, the disruption of which results in disease. Emerging evidence suggests a more direct role for some of these adhesion proteins in chromatin structure and gene regulation, RNA maturation and other non-canonical functions. While many of these discoveries were previously limited to observations of cytoplasmic-nuclear transport, recent advances in microscopy, and biochemical, proteomic and genomic technologies have begun to significantly enhance our understanding of the impact of nuclear localization of these proteins. This review will briefly cover known cell adhesion proteins that migrate to the nucleus, and their downstream functions. We will outline recent advances in this very exciting yet still emerging field, with impact ranging from basic biology to disease states like cancer.
    Language English
    Publishing date 2023-04-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1163553
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Long-Lasting Epigenetic Changes in the Dopamine Transporter in Adult Animals Exposed to Amphetamine during Embryogenesis: Investigating Behavioral Effects.

    Ke, Tao / Ambigapathy, Ganesh / Ton, Thanh / Dhasarathy, Archana / Carvelli, Lucia

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: The dopamine transporter (DAT) is an integral member of the dopaminergic system and is responsible for the release and reuptake of dopamine from the synaptic space into the dopaminergic neurons. DAT is also the major target of amphetamine (Amph). The ... ...

    Abstract The dopamine transporter (DAT) is an integral member of the dopaminergic system and is responsible for the release and reuptake of dopamine from the synaptic space into the dopaminergic neurons. DAT is also the major target of amphetamine (Amph). The effects of Amph on DAT have been intensively studied; however, the mechanisms underlying the long-term effects caused by embryonal exposure to addictive doses of Amph remain largely unexplored. As in mammals, in the nematode
    MeSH term(s) Animals ; Amphetamine/pharmacology ; Dopamine Plasma Membrane Transport Proteins/genetics ; Caenorhabditis elegans/genetics ; Embryonic Development/genetics ; Dopamine ; Epigenesis, Genetic ; Mammals
    Chemical Substances Amphetamine (CK833KGX7E) ; Dopamine Plasma Membrane Transport Proteins ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2023-08-23
    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/ijms241713092
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Investigating pioneer factor activity and its coordination with chromatin remodelers using integrated synthetic oligo assay.

    Chen, Hengye / Yan, Chao / Dhasarathy, Archana / Kladde, Michael / Bai, Lu

    STAR protocols

    2023  Volume 4, Issue 2, Page(s) 102279

    Abstract: Chromatin accessibility is regulated by pioneer factors (PFs) and chromatin remodelers (CRs). Here, we present a protocol, based on integrated synthetic oligonucleotide libraries in yeast, to systematically interrogate the nucleosome-displacing ... ...

    Abstract Chromatin accessibility is regulated by pioneer factors (PFs) and chromatin remodelers (CRs). Here, we present a protocol, based on integrated synthetic oligonucleotide libraries in yeast, to systematically interrogate the nucleosome-displacing activities of PFs and their coordination with CRs. We describe steps for designing oligonucleotide sequences, constructing yeast libraries, measuring nucleosome configurations, and data analyses. This approach potentially can be adapted for use in higher eukaryotes to investigate the activities of many types of chromatin-associated factors. For complete details on the use and execution of this protocol, please refer to Yan et al.,
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Investigating pioneer factor activity and its coordination with chromatin remodelers using integrated synthetic oligo assay

    Hengye Chen / Chao Yan / Archana Dhasarathy / Michael Kladde / Lu Bai

    STAR Protocols, Vol 4, Iss 2, Pp 102279- (2023)

    2023  

    Abstract: Summary: Chromatin accessibility is regulated by pioneer factors (PFs) and chromatin remodelers (CRs). Here, we present a protocol, based on integrated synthetic oligonucleotide libraries in yeast, to systematically interrogate the nucleosome-displacing ... ...

    Abstract Summary: Chromatin accessibility is regulated by pioneer factors (PFs) and chromatin remodelers (CRs). Here, we present a protocol, based on integrated synthetic oligonucleotide libraries in yeast, to systematically interrogate the nucleosome-displacing activities of PFs and their coordination with CRs. We describe steps for designing oligonucleotide sequences, constructing yeast libraries, measuring nucleosome configurations, and data analyses. This approach potentially can be adapted for use in higher eukaryotes to investigate the activities of many types of chromatin-associated factors.For complete details on the use and execution of this protocol, please refer to Yan et al.,1 and Chen et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Genetics ; Genomics ; Biotechnology and bioengineering ; Science (General) ; Q1-390
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Partitioned usage of chromatin remodelers by nucleosome-displacing factors.

    Chen, Hengye / Kharerin, Hungyo / Dhasarathy, Archana / Kladde, Michael / Bai, Lu

    Cell reports

    2022  Volume 40, Issue 8, Page(s) 111250

    Abstract: Nucleosome-displacing-factors (NDFs) in yeast, similar to pioneer factors in higher eukaryotes, can open closed chromatin and generate nucleosome-depleted regions (NDRs). NDRs in yeast are also affected by ATP-dependent chromatin remodelers (CRs). ... ...

    Abstract Nucleosome-displacing-factors (NDFs) in yeast, similar to pioneer factors in higher eukaryotes, can open closed chromatin and generate nucleosome-depleted regions (NDRs). NDRs in yeast are also affected by ATP-dependent chromatin remodelers (CRs). However, how NDFs and CRs coordinate in nucleosome invasion and NDR formation is still unclear. Here, we design a high-throughput method to systematically study the interplay between NDFs and CRs. By combining an integrated synthetic oligonucleotide library with DNA methyltransferase-based, single-molecule nucleosome mapping, we measure the impact of CRs on NDRs generated by individual NDFs. We find that CRs are dispensable for nucleosome invasion by NDFs, and they function downstream of NDF binding to modulate the NDR length. A few CRs show high specificity toward certain NDFs; however, in most cases, CRs are recruited in a factor-nonspecific and NDR length-dependent manner. Overall, our study provides a framework to investigate how NDFs and CRs cooperate to regulate chromatin opening.
    MeSH term(s) Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Nucleosomes/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Chromatin ; Nucleosomes ; Saccharomyces cerevisiae Proteins
    Language English
    Publishing date 2022-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.111250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: ATAC-seq Optimization for Cancer Epigenetics Research.

    Cooper, Mikhala / Ray, Atrayee / Bhattacharya, Atrayee / Dhasarathy, Archana / Takaku, Motoki

    Journal of visualized experiments : JoVE

    2022  , Issue 184

    Abstract: The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) probes deoxyribonucleic acid (DNA) accessibility using the hyperactive Tn5 transposase. Tn5 cuts and ligates adapters for high-throughput sequencing within ... ...

    Abstract The assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) probes deoxyribonucleic acid (DNA) accessibility using the hyperactive Tn5 transposase. Tn5 cuts and ligates adapters for high-throughput sequencing within accessible chromatin regions. In eukaryotic cells, genomic DNA is packaged into chromatin, a complex of DNA, histones, and other proteins, which acts as a physical barrier to the transcriptional machinery. In response to extrinsic signals, transcription factors recruit chromatin remodeling complexes to enable access to the transcriptional machinery for gene activation. Therefore, identifying open chromatin regions is useful when monitoring enhancer and gene promoter activities during biological events such as cancer progression. Since this protocol is easy to use and has a low cell input requirement, ATAC-seq has been widely adopted to define open chromatin regions in various cell types, including cancer cells. For successful data acquisition, several parameters need to be considered when preparing ATAC-seq libraries. Among them, the choice of cell lysis buffer, the titration of the Tn5 enzyme, and the starting volume of cells are crucial for ATAC-seq library preparation in cancer cells. Optimization is essential for generating high-quality data. Here, we provide a detailed description of the ATAC-seq optimization methods for epithelial cell types.
    MeSH term(s) Chromatin/genetics ; Chromatin Immunoprecipitation Sequencing ; DNA/genetics ; Epigenesis, Genetic ; High-Throughput Nucleotide Sequencing/methods ; Neoplasms/genetics ; Sequence Analysis, DNA/methods ; Transcription Factors/metabolism
    Chemical Substances Chromatin ; Transcription Factors ; DNA (9007-49-2)
    Language English
    Publishing date 2022-06-30
    Publishing country United States
    Document type Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/64242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Influence of maternal obesity, diet and exercise on epigenetic regulation of adipocytes.

    Dhasarathy, Archana / Roemmich, James N / Claycombe, Kate J

    Molecular aspects of medicine

    2017  Volume 54, Page(s) 37–49

    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 197640-0
    ISSN 1872-9452 ; 0098-2997
    ISSN (online) 1872-9452
    ISSN 0098-2997
    DOI 10.1016/j.mam.2016.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Influence of maternal obesity, diet and exercise on epigenetic regulation of adipocytes

    Dhasarathy, Archana / Roemmich, James N. / Claycombe, Kate J.

    Molecular Aspects of Medicine. 2017 Apr., v. 54

    2017  

    Abstract: not required for publication. ...

    Abstract not required for publication.
    Keywords adipocytes ; diet ; epigenetics ; exercise ; medicine ; obesity
    Language English
    Dates of publication 2017-04
    Size p. 37-49.
    Publishing place Elsevier BV
    Document type Article
    ZDB-ID 197640-0
    ISSN 1872-9452 ; 0098-2997
    ISSN (online) 1872-9452
    ISSN 0098-2997
    DOI 10.1016/j.mam.2016.10.003
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Connecting the dots: chromatin and alternative splicing in EMT.

    Warns, Jessica A / Davie, James R / Dhasarathy, Archana

    Biochemistry and cell biology = Biochimie et biologie cellulaire

    2016  Volume 94, Issue 1, Page(s) 12–25

    Abstract: Nature has devised sophisticated cellular machinery to process mRNA transcripts produced by RNA Polymerase II, removing intronic regions and connecting exons together, to produce mature RNAs. This process, known as splicing, is very closely linked to ... ...

    Abstract Nature has devised sophisticated cellular machinery to process mRNA transcripts produced by RNA Polymerase II, removing intronic regions and connecting exons together, to produce mature RNAs. This process, known as splicing, is very closely linked to transcription. Alternative splicing, or the ability to produce different combinations of exons that are spliced together from the same genomic template, is a fundamental means of regulating protein complexity. Similar to transcription, both constitutive and alternative splicing can be regulated by chromatin and its associated factors in response to various signal transduction pathways activated by external stimuli. This regulation can vary between different cell types, and interference with these pathways can lead to changes in splicing, often resulting in aberrant cellular states and disease. The epithelial to mesenchymal transition (EMT), which leads to cancer metastasis, is influenced by alternative splicing events of chromatin remodelers and epigenetic factors such as DNA methylation and non-coding RNAs. In this review, we will discuss the role of epigenetic factors including chromatin, chromatin remodelers, DNA methyltransferases, and microRNAs in the context of alternative splicing, and discuss their potential involvement in alternative splicing during the EMT process.
    MeSH term(s) Alternative Splicing ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; DNA Methylation ; Epithelial-Mesenchymal Transition/genetics ; Exons ; Histone Code ; Humans ; Introns ; Neoplasms/chemistry ; Neoplasms/genetics ; Nucleosomes/metabolism ; RNA Polymerase II/metabolism ; RNA Precursors/chemistry ; RNA Precursors/genetics ; RNA, Messenger/genetics ; RNA, Untranslated/chemistry ; RNA, Untranslated/genetics ; Signal Transduction ; Transcription, Genetic
    Chemical Substances Chromatin ; Nucleosomes ; RNA Precursors ; RNA, Messenger ; RNA, Untranslated ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2016-02
    Publishing country Canada
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 54104-7
    ISSN 1208-6002 ; 0829-8211
    ISSN (online) 1208-6002
    ISSN 0829-8211
    DOI 10.1139/bcb-2015-0053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: The Epigenetic Mechanisms of Amphetamine.

    McCowan, Talus J / Dhasarathy, Archana / Carvelli, Lucia

    Journal of addiction & prevention

    2015  Volume 2015, Issue Suppl 1

    Abstract: Amphetamine (AMPH) is a psychostimulant and the most prescribed drug to treat attention deficit hyperactive disorder (ADHD). Although therapeutically used doses are generally well tolerated, numerous side effects are still known to occur, such as ... ...

    Abstract Amphetamine (AMPH) is a psychostimulant and the most prescribed drug to treat attention deficit hyperactive disorder (ADHD). Although therapeutically used doses are generally well tolerated, numerous side effects are still known to occur, such as jitteriness, loss of appetite and psychosis. Moreover, AMPH is liable to be abused by users looking for increased alertness, weight loss or athletic performance. A growing body of evidence indicates that drugs of abuse, including AMPH, control gene expression through chromatin modifications. However, while numerous studies have investigated the molecular mechanisms of AMPH action, only a small number of studies have explored changes in gene expression caused by AMPH. This review examines the epigenetic changes induced by chronic and acute treatments with AMPH and includes, where relevant, data obtained with other psychostimulants such as methamphetamine and cocaine.
    Language English
    Publishing date 2015-02-09
    Publishing country United States
    Document type Journal Article
    ISSN 2330-2178
    ISSN 2330-2178
    DOI 10.13188/2330-2178.S100001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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