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  1. Article ; Online: Live-cell imaging of chromatin contacts opens a new window into chromatin dynamics.

    van Staalduinen, Jente / van Staveren, Thomas / Grosveld, Frank / Wendt, Kerstin S

    Epigenetics & chromatin

    2023  Volume 16, Issue 1, Page(s) 27

    Abstract: Our understanding of the organization of the chromatin fiber within the cell nucleus has made great progress in the last few years. High-resolution techniques based on next-generation sequencing as well as optical imaging that can investigate chromatin ... ...

    Abstract Our understanding of the organization of the chromatin fiber within the cell nucleus has made great progress in the last few years. High-resolution techniques based on next-generation sequencing as well as optical imaging that can investigate chromatin conformations down to the single cell level have revealed that chromatin structure is highly heterogeneous at the level of the individual allele. While TAD boundaries and enhancer-promoter pairs emerge as hotspots of 3D proximity, the spatiotemporal dynamics of these different types of chromatin contacts remain largely unexplored. Investigation of chromatin contacts in live single cells is necessary to close this knowledge gap and further enhance the current models of 3D genome organization and enhancer-promoter communication. In this review, we first discuss the potential of single locus labeling to study architectural and enhancer-promoter contacts and provide an overview of the available single locus labeling techniques such as FROS, TALE, CRISPR-dCas9 and ANCHOR, and discuss the latest developments and applications of these systems.
    MeSH term(s) Chromatin/metabolism ; Cell Nucleus/metabolism ; Genome
    Chemical Substances Chromatin
    Language English
    Publishing date 2023-06-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2462129-8
    ISSN 1756-8935 ; 1756-8935
    ISSN (online) 1756-8935
    ISSN 1756-8935
    DOI 10.1186/s13072-023-00503-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Transcriptional Regulation by (Super)Enhancers: From Discovery to Mechanisms.

    Grosveld, Frank / van Staalduinen, Jente / Stadhouders, Ralph

    Annual review of genomics and human genetics

    2021  Volume 22, Page(s) 127–146

    Abstract: Accurate control of gene expression in the right cell at the right moment is of fundamental importance to animal development and homeostasis. At the heart of gene regulation lie the enhancers, a class of gene regulatory elements that ensures precise ... ...

    Abstract Accurate control of gene expression in the right cell at the right moment is of fundamental importance to animal development and homeostasis. At the heart of gene regulation lie the enhancers, a class of gene regulatory elements that ensures precise spatiotemporal activation of gene transcription. Mammalian genomes are littered with enhancers, which are frequently organized in cooperative clusters such as locus control regions and superenhancers. Here, we discuss our current knowledge of enhancer biology, including an overview of the discovery of the various enhancer subsets and the mechanistic models used to explain their gene regulatory function.
    MeSH term(s) Animals ; Chromatin ; Enhancer Elements, Genetic ; Gene Expression Regulation ; Humans
    Chemical Substances Chromatin
    Language English
    Publishing date 2021-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2037670-4
    ISSN 1545-293X ; 1527-8204
    ISSN (online) 1545-293X
    ISSN 1527-8204
    DOI 10.1146/annurev-genom-122220-093818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Compartmentalization of androgen receptors at endogenous genes in living cells.

    Yavuz, Selçuk / Kabbech, Hélène / van Staalduinen, Jente / Linder, Simon / van Cappellen, Wiggert A / Nigg, Alex L / Abraham, Tsion E / Slotman, Johan A / Quevedo, Marti / Poot, Raymond A / Zwart, Wilbert / van Royen, Martin E / Grosveld, Frank G / Smal, Ihor / Houtsmuller, Adriaan B

    Nucleic acids research

    2023  Volume 51, Issue 20, Page(s) 10992–11009

    Abstract: A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, ... ...

    Abstract A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.
    MeSH term(s) Animals ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Nuclear Proteins/metabolism ; Receptors, Androgen/metabolism ; Humans ; Mice ; Cell Line, Tumor
    Chemical Substances Nuclear Proteins ; Receptors, Androgen
    Language English
    Publishing date 2023-10-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad803
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Epithelial-mesenchymal-transition-inducing transcription factors: new targets for tackling chemoresistance in cancer?

    van Staalduinen, Jente / Baker, David / Ten Dijke, Peter / van Dam, Hans

    Oncogene

    2018  Volume 37, Issue 48, Page(s) 6195–6211

    Abstract: Chemoresistance remains a major complication of cancer treatments. Recent data provide strong evidence that chemoresistance is linked to epithelial-mesenchymal transition (EMT), a latent developmental process, which is re-activated during cancer ... ...

    Abstract Chemoresistance remains a major complication of cancer treatments. Recent data provide strong evidence that chemoresistance is linked to epithelial-mesenchymal transition (EMT), a latent developmental process, which is re-activated during cancer progression. EMT involves transcriptional reprogramming and is driven by specific EMT transcription factors (EMT-TFs). In this review, we provide support for the idea that EMT-TFs contribute to the development of resistance against cancer therapy and discuss how EMT-TFs might be targeted to advance novel therapeutic approaches to the treatment of cancer.
    MeSH term(s) Animals ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/physiology ; Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/physiology ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2018-07-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-018-0378-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis.

    Giraud, Guillaume / Kolovos, Petros / Boltsis, Ilias / van Staalduinen, Jente / Guyot, Boris / Weiss-Gayet, Michele / IJcken, Wilfred van / Morlé, François / Grosveld, Frank

    iScience

    2021  Volume 24, Issue 3, Page(s) 102210

    Abstract: Transcription factors are key players in a broad range of cellular processes such as cell-fate decision. Understanding how they act to control these processes is of critical importance for therapy purposes. FLI-1 controls several hematopoietic lineage ... ...

    Abstract Transcription factors are key players in a broad range of cellular processes such as cell-fate decision. Understanding how they act to control these processes is of critical importance for therapy purposes. FLI-1 controls several hematopoietic lineage differentiation including megakaryopoiesis and erythropoiesis. Its aberrant expression is often observed in cancer and is associated with poor prognosis. We showed that FLI-1 interacts with the LDB1 complex, which also plays critical roles in erythropoiesis and megakaryopoiesis. In this study, we aimed to unravel how FLI-1 and the LDB1 complex act together in murine erythroleukemia cells and in megakaryocyte. Combining omics techniques, we show that FLI-1 enables the recruitment of the LDB1 complex to regulatory sequences of megakaryocytic genes and to enhancers. We show as well for the first time that FLI-1 is able to modulate the 3D chromatin organization by promoting chromatin looping between enhancers and promoters most likely through the LDB1 complex.
    Language English
    Publishing date 2021-02-20
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2021.102210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The effect of aspirin and nonsteroidal anti-inflammatory drug use after diagnosis on survival of oesophageal cancer patients.

    van Staalduinen, Jente / Frouws, Martine / Reimers, Marlies / Bastiaannet, Esther / van Herk-Sukel, Myrthe P P / Lemmens, Valery / de Steur, Wobbe O / Hartgrink, Henk H / van de Velde, Cornelis J H / Liefers, Gerrit-Jan

    British journal of cancer

    2016  Volume 114, Issue 9, Page(s) 1053–1059

    Abstract: Background: Aspirin use has been shown to lower incidence and mortality in cancer patients. The aim of this population-based study was to determine the effect of postdiagnosis low-dose aspirin use on survival of patients with oesophageal cancer.: ... ...

    Abstract Background: Aspirin use has been shown to lower incidence and mortality in cancer patients. The aim of this population-based study was to determine the effect of postdiagnosis low-dose aspirin use on survival of patients with oesophageal cancer.
    Methods: Patients with oesophageal cancer (1998-2010) were selected from the Eindhoven Cancer Registry and linked with outpatient pharmacy data regarding aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Users were subdivided into both prediagnosis and postdiagnosis or only postdiagnosis users. Parametric survival models with an exponential (Poisson) distribution were used with non-specific death as endpoint.
    Results: In this study 560 patients were included. Overall, 157 patients (28.0%) were non-users, 293 patients (52.3%) pre- and postdiagnosis (89 aspirin and 204 NSAID users) and 110 patients (19.6%) only postdiagnosis users (16 aspirin and 94 NSAID users). Postdiagnosis aspirin use was associated with overall survival (RR 0.45 (95% CI 0.34-0.60; P<0.001); adjusted rate ratio was 0.42 (95% CI: 0.30-0.57; P<0.001). Postdiagnosis use of NSAIDs was associated with overall survival (RR 0.61 (95% CI 0.49-0.76; <0.001); however, adjusted analyses did not show a significant association with a rate ratio of 0.84 (95% CI 0.66-1.07; P=0.2).
    Conclusions: Our study shows that postdiagnosis aspirin use might be associated with a higher survival rate in oesophageal cancer patients. A randomised clinical trial is needed to verify our observations of possible postdiagnosis aspirin use benefit.
    MeSH term(s) Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Aspirin/therapeutic use ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/mortality ; Female ; Humans ; Middle Aged ; Risk Assessment ; Survival Rate
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2016-04-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/bjc.2016.65
    Database MEDical Literature Analysis and Retrieval System OnLINE

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