LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 5 of total 5

Search options

  1. Article ; Online: Chromatin regulation of transcriptional enhancers and cell fate by the Sotos syndrome gene NSD1

    Sun, Zhen / Lin, Yuan / Islam, Mohammed T. / Koche, Richard / Hedehus, Lin / Liu, Dingyu / Huang, Chang / Vierbuchen, Thomas / Sawyers, Charles L. / Helin, Kristian

    Molecular Cell. 20232023 July 03, July 03, v. 83, no. 14 p.2398-2416.e12

    2023  

    Abstract: Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 ... ...

    Abstract Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 and DNA methylation, the direct role of NSD1 in transcriptional regulation remains largely unknown. Here, we show that NSD1 and H3K36me2 are enriched at cis-regulatory elements, particularly enhancers. NSD1 enhancer association is conferred by a tandem quadruple PHD (qPHD)-PWWP module, which recognizes p300-catalyzed H3K18ac. By combining acute NSD1 depletion with time-resolved epigenomic and nascent transcriptomic analyses, we demonstrate that NSD1 promotes enhancer-dependent gene transcription by facilitating RNA polymerase II (RNA Pol II) pause release. Notably, NSD1 can act as a transcriptional coactivator independent of its catalytic activity. Moreover, NSD1 enables the activation of developmental transcriptional programs associated with Sotos syndrome pathophysiology and controls embryonic stem cell (ESC) multilineage differentiation. Collectively, we have identified NSD1 as an enhancer-acting transcriptional coactivator that contributes to cell fate transition and Sotos syndrome development.
    Keywords DNA methylation ; DNA-directed RNA polymerase ; RNA ; catalytic activity ; cell differentiation ; chromatin ; embryonic stem cells ; epigenome ; genes ; mammals ; methyltransferases ; pathophysiology ; transcription (genetics) ; transcriptomics ; enhancers ; NSD1 ; H3K36 methylation ; histone methylation ; gene expression ; Sotos syndrome ; stem cells ; reader domain ; Pol II pause release
    Language English
    Dates of publication 2023-0703
    Size p. 2398-2416.e12.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2023.06.007
    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.

  2. Article ; Online: Chromatin regulation of transcriptional enhancers and cell fate by the Sotos syndrome gene NSD1.

    Sun, Zhen / Lin, Yuan / Islam, Mohammed T / Koche, Richard / Hedehus, Lin / Liu, Dingyu / Huang, Chang / Vierbuchen, Thomas / Sawyers, Charles L / Helin, Kristian

    Molecular cell

    2023  Volume 83, Issue 14, Page(s) 2398–2416.e12

    Abstract: Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 ... ...

    Abstract Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 and DNA methylation, the direct role of NSD1 in transcriptional regulation remains largely unknown. Here, we show that NSD1 and H3K36me2 are enriched at cis-regulatory elements, particularly enhancers. NSD1 enhancer association is conferred by a tandem quadruple PHD (qPHD)-PWWP module, which recognizes p300-catalyzed H3K18ac. By combining acute NSD1 depletion with time-resolved epigenomic and nascent transcriptomic analyses, we demonstrate that NSD1 promotes enhancer-dependent gene transcription by facilitating RNA polymerase II (RNA Pol II) pause release. Notably, NSD1 can act as a transcriptional coactivator independent of its catalytic activity. Moreover, NSD1 enables the activation of developmental transcriptional programs associated with Sotos syndrome pathophysiology and controls embryonic stem cell (ESC) multilineage differentiation. Collectively, we have identified NSD1 as an enhancer-acting transcriptional coactivator that contributes to cell fate transition and Sotos syndrome development.
    MeSH term(s) Animals ; Humans ; Nuclear Proteins/metabolism ; Chromatin ; Sotos Syndrome/genetics ; Sotos Syndrome/metabolism ; Histone Methyltransferases/genetics ; Transcription Factors/genetics ; Cell Differentiation/genetics ; Mammals/metabolism ; Histone-Lysine N-Methyltransferase/genetics
    Chemical Substances Nuclear Proteins ; Chromatin ; Histone Methyltransferases (EC 2.1.1.-) ; Transcription Factors ; NSD1 protein, human (EC 2.1.1.43) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43)
    Language English
    Publishing date 2023-07-03
    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.2023.06.007
    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: Non-core Subunits of the PRC2 Complex Are Collectively Required for Its Target-Site Specificity

    Højfeldt, Jonas Westergaard / Hedehus, Lin / Laugesen, Anne / Tatar, Tülin / Wiehle, Laura / Helin, Kristian

    Molecular cell. 2019 Nov. 07, v. 76, no. 3

    2019  

    Abstract: The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, ... ...

    Abstract The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, understanding the delineation of genome-wide H3K27 methylation patterns has been the focus of intense investigation. PRC2 methylation activity is abundant and dispersed throughout the genome, but the highest activity is specifically directed to a subset of target sites that are stably occupied by the complex and highly enriched for H3K27me3. Here, we show, by systematically knocking out single and multiple non-core subunits of the PRC2 complex in mouse embryonic stem cells, that they each contribute to directing PRC2 activity to target sites. Furthermore, combined knockout of six non-core subunits reveals that, while dispensable for global H3K27 methylation levels, the non-core PRC2 subunits are collectively required for focusing H3K27me3 activity to specific sites in the genome.
    Keywords catalytic activity ; embryonic stem cells ; genome ; methylation ; mice ; neoplasms ; transcription (genetics)
    Language English
    Dates of publication 2019-1107
    Size p. 423-436.e3.
    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.2019.07.031
    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: Non-core Subunits of the PRC2 Complex Are Collectively Required for Its Target-Site Specificity.

    Højfeldt, Jonas Westergaard / Hedehus, Lin / Laugesen, Anne / Tatar, Tülin / Wiehle, Laura / Helin, Kristian

    Molecular cell

    2019  Volume 76, Issue 3, Page(s) 423–436.e3

    Abstract: The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, ... ...

    Abstract The Polycomb repressive complex 2 (PRC2) catalyzes H3K27 methylation across the genome, which impacts transcriptional regulation and is critical for establishment of cell identity. Because of its essential function during development and in cancer, understanding the delineation of genome-wide H3K27 methylation patterns has been the focus of intense investigation. PRC2 methylation activity is abundant and dispersed throughout the genome, but the highest activity is specifically directed to a subset of target sites that are stably occupied by the complex and highly enriched for H3K27me3. Here, we show, by systematically knocking out single and multiple non-core subunits of the PRC2 complex in mouse embryonic stem cells, that they each contribute to directing PRC2 activity to target sites. Furthermore, combined knockout of six non-core subunits reveals that, while dispensable for global H3K27 methylation levels, the non-core PRC2 subunits are collectively required for focusing H3K27me3 activity to specific sites in the genome.
    MeSH term(s) Animals ; Cell Line ; DNA Methylation ; Gene Silencing ; Histones/genetics ; Histones/metabolism ; Male ; Methylation ; Mice ; Mouse Embryonic Stem Cells/metabolism ; Polycomb Repressive Complex 2/chemistry ; Polycomb Repressive Complex 2/genetics ; Polycomb Repressive Complex 2/metabolism ; Protein Conformation ; Protein Processing, Post-Translational ; Protein Subunits ; Structure-Activity Relationship
    Chemical Substances Histones ; Protein Subunits ; Suz12 protein, mouse ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
    Language English
    Publishing date 2019-09-11
    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.2019.07.031
    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.

  5. Article ; Online: Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2.

    Højfeldt, Jonas W / Laugesen, Anne / Willumsen, Berthe M / Damhofer, Helene / Hedehus, Lin / Tvardovskiy, Andrey / Mohammad, Faizaan / Jensen, Ole N / Helin, Kristian

    Nature structural & molecular biology

    2018  Volume 25, Issue 3, Page(s) 225–232

    Abstract: Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 ... ...

    Abstract Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 methylation patterns remain incompletely understood. Epigenetic mechanisms have been proposed, wherein pre-existing H3K27 methylation directs recruitment and regulates the catalytic activity of PRC2 to support its own maintenance. Here we investigate whether such mechanisms are required for specifying H3K27 methylation patterns in mouse embryonic stem cells (mESCs). Through re-expression of PRC2 subunits in PRC2-knockout cells that have lost all H3K27 methylation, we demonstrate that methylation patterns can be accurately established de novo. We find that regional methylation kinetics correlate with original methylation patterns even in their absence, and specification of the genomic PRC2 binding pattern is retained and specifically dependent on the PRC2 core subunit SUZ12. Thus, the H3K27 methylation patterns in mESCs are not dependent on self-autonomous epigenetic inheritance.
    MeSH term(s) Animals ; Cells, Cultured ; CpG Islands ; Embryonic Stem Cells/metabolism ; Histones/metabolism ; Kinetics ; Methylation ; Mice ; Polycomb Repressive Complex 2/metabolism
    Chemical Substances Histones ; Suz12 protein, mouse ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
    Language English
    Publishing date 2018-02-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-018-0036-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4101: 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)
    Zs.MG 56: 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.

To top