LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: DisP-seq reveals the genome-wide functional organization of DNA-associated disordered proteins.

    Xing, Yu-Hang / Dong, Rui / Lee, Lukuo / Rengarajan, Shruthi / Riggi, Nicolò / Boulay, Gaylor / Rivera, Miguel N

    Nature biotechnology

    2023  Volume 42, Issue 1, Page(s) 52–64

    Abstract: Intrinsically disordered regions (IDRs) in DNA-associated proteins are known to influence gene regulation, but their distribution and cooperative functions in genome-wide regulatory programs remain poorly understood. Here we describe DisP-seq (disordered ...

    Abstract Intrinsically disordered regions (IDRs) in DNA-associated proteins are known to influence gene regulation, but their distribution and cooperative functions in genome-wide regulatory programs remain poorly understood. Here we describe DisP-seq (disordered protein precipitation followed by DNA sequencing), an antibody-independent chemical precipitation assay that can simultaneously map endogenous DNA-associated disordered proteins genome-wide through a combination of biotinylated isoxazole precipitation and next-generation sequencing. DisP-seq profiles are composed of thousands of peaks that are associated with diverse chromatin states, are enriched for disordered transcription factors (TFs) and are often arranged in large lineage-specific clusters with high local concentrations of disordered proteins and different combinations of histone modifications linked to regulatory potential. We use DisP-seq to analyze cancer cells and reveal how disordered protein-associated islands enable IDR-dependent mechanisms that control the binding and function of disordered TFs, including oncogene-dependent sequestration of TFs through long-range interactions and the reactivation of differentiation pathways upon loss of oncogenic stimuli in Ewing sarcoma.
    MeSH term(s) DNA ; Chromatin ; Sequence Analysis, DNA
    Chemical Substances DNA (9007-49-2) ; Chromatin
    Language English
    Publishing date 2023-04-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-023-01737-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2167: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 137: Show issues
    Zs.MG 43: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Condensates induced by transcription inhibition localize active chromatin to nucleoli.

    Yasuhara, Takaaki / Xing, Yu-Hang / Bauer, Nicholas C / Lee, Lukuo / Dong, Rui / Yadav, Tribhuwan / Soberman, Roy J / Rivera, Miguel N / Zou, Lee

    Molecular cell

    2022  Volume 82, Issue 15, Page(s) 2738–2753.e6

    Abstract: The proper function of the genome relies on spatial organization of DNA, RNA, and proteins, but how transcription contributes to the organization is unclear. Here, we show that condensates induced by transcription inhibition (CITIs) drastically alter ... ...

    Abstract The proper function of the genome relies on spatial organization of DNA, RNA, and proteins, but how transcription contributes to the organization is unclear. Here, we show that condensates induced by transcription inhibition (CITIs) drastically alter genome spatial organization. CITIs are formed by SFPQ, NONO, FUS, and TAF15 in nucleoli upon inhibition of RNA polymerase II (RNAPII). Mechanistically, RNAPII inhibition perturbs ribosomal RNA (rRNA) processing, releases rRNA-processing factors from nucleoli, and enables SFPQ to bind rRNA. While accumulating in CITIs, SFPQ/TAF15 remain associated with active genes and tether active chromatin to nucleoli. In the presence of DNA double-strand breaks (DSBs), the altered chromatin compartmentalization induced by RNAPII inhibition increases gene fusions in CITIs and stimulates the formation of fusion oncogenes. Thus, proper RNAPII transcription and rRNA processing prevent the altered compartmentalization of active chromatin in CITIs, suppressing the generation of gene fusions from DSBs.
    MeSH term(s) Cell Nucleolus/genetics ; Cell Nucleolus/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; DNA Breaks, Double-Stranded ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA, Ribosomal/genetics ; RNA, Ribosomal/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; RNA, Ribosomal ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2022-06-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2022.05.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5055: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: Condensates induced by transcription inhibition localize active chromatin to nucleoli

    Yasuhara, Takaaki / Xing, Yu-Hang / Bauer, Nicholas C. / Lee, Lukuo / Dong, Rui / Yadav, Tribhuwan / Soberman, Roy J. / Rivera, Miguel N. / Zou, Lee

    Molecular cell. 2022 Aug. 04, v. 82, no. 15

    2022  

    Abstract: The proper function of the genome relies on spatial organization of DNA, RNA, and proteins, but how transcription contributes to the organization is unclear. Here, we show that condensates induced by transcription inhibition (CITIs) drastically alter ... ...

    Abstract The proper function of the genome relies on spatial organization of DNA, RNA, and proteins, but how transcription contributes to the organization is unclear. Here, we show that condensates induced by transcription inhibition (CITIs) drastically alter genome spatial organization. CITIs are formed by SFPQ, NONO, FUS, and TAF15 in nucleoli upon inhibition of RNA polymerase II (RNAPII). Mechanistically, RNAPII inhibition perturbs ribosomal RNA (rRNA) processing, releases rRNA-processing factors from nucleoli, and enables SFPQ to bind rRNA. While accumulating in CITIs, SFPQ/TAF15 remain associated with active genes and tether active chromatin to nucleoli. In the presence of DNA double-strand breaks (DSBs), the altered chromatin compartmentalization induced by RNAPII inhibition increases gene fusions in CITIs and stimulates the formation of fusion oncogenes. Thus, proper RNAPII transcription and rRNA processing prevent the altered compartmentalization of active chromatin in CITIs, suppressing the generation of gene fusions from DSBs.
    Keywords DNA ; DNA-directed RNA polymerase ; chromatin ; oncogenes ; ribosomal RNA
    Language English
    Dates of publication 2022-0804
    Size p. 2738-2753.e6.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2022.05.010
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 2005/501: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Highly connected 3D chromatin networks established by an oncogenic fusion protein shape tumor cell identity.

    Sanalkumar, Rajendran / Dong, Rui / Lee, Lukuo / Xing, Yu-Hang / Iyer, Sowmya / Letovanec, Igor / La Rosa, Stefano / Finzi, Giovanna / Musolino, Elettra / Papait, Roberto / Chebib, Ivan / Nielsen, G Petur / Renella, Raffaele / Cote, Gregory M / Choy, Edwin / Aryee, Martin / Stegmaier, Kimberly / Stamenkovic, Ivan / Rivera, Miguel N /
    Riggi, Nicolò

    Science advances

    2023  Volume 9, Issue 13, Page(s) eabo3789

    Abstract: Cell fate transitions observed in embryonic development involve changes in three-dimensional genomic organization that provide proper lineage specification. Whether similar events occur within tumor cells and contribute to cancer evolution remains ... ...

    Abstract Cell fate transitions observed in embryonic development involve changes in three-dimensional genomic organization that provide proper lineage specification. Whether similar events occur within tumor cells and contribute to cancer evolution remains largely unexplored. We modeled this process in the pediatric cancer Ewing sarcoma and investigated high-resolution looping and large-scale nuclear conformation changes associated with the oncogenic fusion protein EWS-FLI1. We show that chromatin interactions in tumor cells are dominated by highly connected looping hubs centered on EWS-FLI1 binding sites, which directly control the activity of linked enhancers and promoters to establish oncogenic expression programs. Conversely, EWS-FLI1 depletion led to the disassembly of these looping networks and a widespread nuclear reorganization through the establishment of new looping patterns and large-scale compartment configuration matching those observed in mesenchymal stem cells, a candidate Ewing sarcoma progenitor. Our data demonstrate that major architectural features of nuclear organization in cancer cells can depend on single oncogenes and are readily reversed to reestablish latent differentiation programs.
    MeSH term(s) Child ; Humans ; Sarcoma, Ewing/genetics ; Sarcoma, Ewing/metabolism ; Sarcoma, Ewing/pathology ; Chromatin/genetics ; Cell Line, Tumor ; RNA-Binding Protein EWS/genetics ; RNA-Binding Protein EWS/metabolism ; Binding Sites ; Cell Differentiation ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Gene Expression Regulation, Neoplastic
    Chemical Substances Chromatin ; RNA-Binding Protein EWS ; Oncogene Proteins, Fusion
    Language English
    Publishing date 2023-03-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abo3789
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors.

    Tak, Y Esther / Boulay, Gaylor / Lee, Lukuo / Iyer, Sowmya / Perry, Nicholas T / Schultz, Hayley T / Garcia, Sara P / Broye, Liliane / Horng, Joy E / Rengarajan, Shruthi / Naigles, Beverly / Volorio, Angela / Sander, Jeffry D / Gong, Jingyi / Riggi, Nicolὸ / Joung, J Keith / Rivera, Miguel N

    Cell genomics

    2020  Volume 2, Issue 4

    Abstract: Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA- ... ...

    Abstract Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA-repeat-targeted engineered zinc finger arrays (ZFAs) can function at least as efficiently as EWS-FLI1 for converting hundreds of GGAA repeats into active enhancers in a Ewing sarcoma precursor cell model. Furthermore, a fusion of a KRAB domain to a ZFA can silence GGAA microsatellite enhancers genome wide in Ewing sarcoma cells, thereby reducing expression of EWS-FLI1-activated genes. Remarkably, this KRAB-ZFA fusion showed selective toxicity against Ewing sarcoma cells compared with non-Ewing cancer cells, consistent with its Ewing sarcoma-specific impact on the transcriptome. These findings demonstrate the value of ZFAs for functional annotation of repeats and illustrate how aberrant microsatellite activities might be regulated for potential therapeutic applications.
    Language English
    Publishing date 2020-10-12
    Publishing country United States
    Document type Journal Article
    ISSN 2666-979X
    ISSN (online) 2666-979X
    DOI 10.1016/j.xgen.2022.100119
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.

    Möller, Emely / Praz, Viviane / Rajendran, Sanalkumar / Dong, Rui / Cauderay, Alexandra / Xing, Yu-Hang / Lee, Lukuo / Fusco, Carlo / Broye, Liliane C / Cironi, Luisa / Iyer, Sowmya / Rengarajan, Shruthi / Awad, Mary E / Naigles, Beverly / Letovanec, Igor / Ormas, Nicola / Finzi, Giovanna / La Rosa, Stefano / Sessa, Fausto /
    Chebib, Ivan / Petur Nielsen, G / Digklia, Antonia / Spentzos, Dimitrios / Cote, Gregory M / Choy, Edwin / Aryee, Martin / Stamenkovic, Ivan / Boulay, Gaylor / Rivera, Miguel N / Riggi, Nicolò

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2267

    Abstract: Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex ... ...

    Abstract Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs in permissive precursor cells. Here we define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma, an aggressive cancer driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 displays a distinct DNA binding pattern that requires the EWSR1 domain and promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures observed in primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of regulatory circuits that promote neural crest-related developmental programs. Taken together, our study elucidates the epigenetic mechanisms utilized by EWSR1-ATF1 to establish regulatory networks in CCS, and points to precursor cells in the neural crest lineage as candidate cells of origin for these tumors.
    MeSH term(s) Carcinogenesis/genetics ; Chromatin/genetics ; Humans ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Oncogenes ; RNA-Binding Protein EWS/genetics ; Sarcoma, Clear Cell/genetics ; Sarcoma, Clear Cell/pathology ; Soft Tissue Neoplasms/genetics
    Chemical Substances Chromatin ; EWSR1 protein, human ; EWSR1-ATF1 fusion protein, human ; Oncogene Proteins, Fusion ; RNA-Binding Protein EWS
    Language English
    Publishing date 2022-04-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29910-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: The chromatin landscape of primary synovial sarcoma organoids is linked to specific epigenetic mechanisms and dependencies.

    Boulay, Gaylor / Cironi, Luisa / Garcia, Sara P / Rengarajan, Shruthi / Xing, Yu-Hang / Lee, Lukuo / Awad, Mary E / Naigles, Beverly / Iyer, Sowmya / Broye, Liliane C / Keskin, Tugba / Cauderay, Alexandra / Fusco, Carlo / Letovanec, Igor / Chebib, Ivan / Nielsen, Petur Gunnalugur / Tercier, Stéphane / Cherix, Stéphane / Nguyen-Ngoc, Tu /
    Cote, Gregory / Choy, Edwin / Provero, Paolo / Suvà, Mario L / Rivera, Miguel N / Stamenkovic, Ivan / Riggi, Nicolò

    Life science alliance

    2020  Volume 4, Issue 2

    Abstract: Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in the in-frame fusion of the BAF complex ... ...

    Abstract Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in the in-frame fusion of the BAF complex gene
    MeSH term(s) Binding Sites ; Chromatin/genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Humans ; Multiprotein Complexes/metabolism ; Organoids ; Protein Binding ; Protein Transport ; Sarcoma, Synovial/genetics ; Sarcoma, Synovial/metabolism ; Transcriptome
    Chemical Substances BANF1 protein, human ; Chromatin ; DNA-Binding Proteins ; Histones ; Multiprotein Complexes
    Language English
    Publishing date 2020-12-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2575-1077
    ISSN (online) 2575-1077
    DOI 10.26508/lsa.202000808
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top