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  1. Article ; Online: Epigenetic memory of cell fate commitment.

    Elsherbiny, Adel / Dobreva, Gergana

    Current opinion in cell biology

    2021  Volume 69, Page(s) 80–87

    Abstract: During development, discrete cell fates are established in precise spatiotemporal order guided by morphogen signals. These signals converge in the nucleus to induce transcriptional and epigenetic programming that determines cell fate. Once cell identity ... ...

    Abstract During development, discrete cell fates are established in precise spatiotemporal order guided by morphogen signals. These signals converge in the nucleus to induce transcriptional and epigenetic programming that determines cell fate. Once cell identity is established, cell programs have to be accurately sustained through multiple rounds of cell division, during which DNA replication serves as a window of opportunity for altering cell fate. In this review, we summarize recent advances in understanding the molecular players that underlie epigenetic memory of cell fate decisions, with a particular focus on histone modifications and mitotic bookmarking factors. We also discuss the different mechanisms of inheritance of repressed and active chromatin states.
    MeSH term(s) Cell Differentiation ; Cell Plasticity ; Chromatin ; Chromatin Assembly and Disassembly ; Epigenesis, Genetic ; Histones/metabolism ; Humans
    Chemical Substances Chromatin ; Histones
    Language English
    Publishing date 2021-01-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2020.12.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2963: 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)

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  2. Article ; Online: Leveraging chromatin state transitions for the identification of regulatory networks orchestrating heart regeneration.

    Cordero, Julio / Elsherbiny, Adel / Wang, Yinuo / Jürgensen, Lonny / Constanty, Florian / Günther, Stefan / Boerries, Melanie / Heineke, Joerg / Beisaw, Arica / Leuschner, Florian / Hassel, David / Dobreva, Gergana

    Nucleic acids research

    2024  Volume 52, Issue 8, Page(s) 4215–4233

    Abstract: The limited regenerative capacity of the human heart contributes to high morbidity and mortality worldwide. In contrast, zebrafish exhibit robust regenerative capacity, providing a powerful model for studying how to overcome intrinsic epigenetic barriers ...

    Abstract The limited regenerative capacity of the human heart contributes to high morbidity and mortality worldwide. In contrast, zebrafish exhibit robust regenerative capacity, providing a powerful model for studying how to overcome intrinsic epigenetic barriers maintaining cardiac homeostasis and initiate regeneration. Here, we present a comprehensive analysis of the histone modifications H3K4me1, H3K4me3, H3K27me3 and H3K27ac during various stages of zebrafish heart regeneration. We found a vast gain of repressive chromatin marks one day after myocardial injury, followed by the acquisition of active chromatin characteristics on day four and a transition to a repressive state on day 14, and identified distinct transcription factor ensembles associated with these events. The rapid transcriptional response involves the engagement of super-enhancers at genes implicated in extracellular matrix reorganization and TOR signaling, while H3K4me3 breadth highly correlates with transcriptional activity and dynamic changes at genes involved in proteolysis, cell cycle activity, and cell differentiation. Using loss- and gain-of-function approaches, we identified transcription factors in cardiomyocytes and endothelial cells influencing cardiomyocyte dedifferentiation or proliferation. Finally, we detected significant evolutionary conservation between regulatory regions that drive zebrafish and neonatal mouse heart regeneration, suggesting that reactivating transcriptional and epigenetic networks converging on these regulatory elements might unlock the regenerative potential of adult human hearts.
    MeSH term(s) Zebrafish/genetics ; Animals ; Regeneration/genetics ; Chromatin/metabolism ; Chromatin/genetics ; Histones/metabolism ; Heart ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/cytology ; Gene Regulatory Networks ; Mice ; Humans ; Epigenesis, Genetic ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Histone Code ; Cell Differentiation/genetics
    Chemical Substances Chromatin ; Histones ; Transcription Factors
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    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/gkae085
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1067: 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)

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  3. Article ; Online: Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function.

    Wang, Yinuo / Elsherbiny, Adel / Kessler, Linda / Cordero, Julio / Shi, Haojie / Serke, Heike / Lityagina, Olga / Trogisch, Felix A / Mohammadi, Mona Malek / El-Battrawy, Ibrahim / Backs, Johannes / Wieland, Thomas / Heineke, Joerg / Dobreva, Gergana

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 6663

    Abstract: Tight control of cell fate choices is crucial for normal development. Here we show that lamin A/C plays a key role in chromatin organization in embryonic stem cells (ESCs), which safeguards naïve pluripotency and ensures proper cell fate choices during ... ...

    Abstract Tight control of cell fate choices is crucial for normal development. Here we show that lamin A/C plays a key role in chromatin organization in embryonic stem cells (ESCs), which safeguards naïve pluripotency and ensures proper cell fate choices during cardiogenesis. We report changes in chromatin compaction and localization of cardiac genes in Lmna-/- ESCs resulting in precocious activation of a transcriptional program promoting cardiomyocyte versus endothelial cell fate. This is accompanied by premature cardiomyocyte differentiation, cell cycle withdrawal and abnormal contractility. Gata4 is activated by lamin A/C loss and Gata4 silencing or haploinsufficiency rescues the aberrant cardiovascular cell fate choices induced by lamin A/C deficiency. We uncover divergent functions of lamin A/C in naïve pluripotent stem cells and cardiomyocytes, which have distinct contributions to the transcriptional alterations of patients with LMNA-associated cardiomyopathy. We conclude that disruption of lamin A/C-dependent chromatin architecture in ESCs is a primary event in LMNA loss-of-function cardiomyopathy.
    MeSH term(s) Humans ; Lamin Type A/metabolism ; Chromatin/metabolism ; Cell Differentiation/genetics ; Embryonic Stem Cells/metabolism ; Myocytes, Cardiac/metabolism
    Chemical Substances Lamin Type A ; Chromatin
    Language English
    Publishing date 2022-11-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-34366-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Endothelial cells drive organ fibrosis in mice by inducing expression of the transcription factor SOX9.

    Trogisch, Felix A / Abouissa, Aya / Keles, Merve / Birke, Anne / Fuhrmann, Manuela / Dittrich, Gesine M / Weinzierl, Nina / Wink, Elvira / Cordero, Julio / Elsherbiny, Adel / Martin-Garrido, Abel / Grein, Steve / Hemanna, Shruthi / Hofmann, Ellen / Nicin, Luka / Bibli, Sofia-Iris / Airik, Rannar / Kispert, Andreas / Kist, Ralf /
    Quanchao, Sun / Kürschner, Sina W / Winkler, Manuel / Gretz, Norbert / Mogler, Carolin / Korff, Thomas / Koch, Philipp-Sebastian / Dimmeler, Stefanie / Dobreva, Gergana / Heineke, Joerg

    Science translational medicine

    2024  Volume 16, Issue 736, Page(s) eabq4581

    Abstract: Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it is unclear to what extent endothelial cells also might contribute. We detected increased expression of the transcription ... ...

    Abstract Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it is unclear to what extent endothelial cells also might contribute. We detected increased expression of the transcription factor
    MeSH term(s) Animals ; Humans ; Mice ; Disease Models, Animal ; Endothelial Cells ; Fibrosis ; Heart Failure ; Intercellular Signaling Peptides and Proteins ; Liver Cirrhosis/complications ; SOX9 Transcription Factor/genetics ; Transcription Factors
    Chemical Substances Intercellular Signaling Peptides and Proteins ; SOX9 protein, human ; SOX9 Transcription Factor ; Transcription Factors ; Sox9 protein, mouse
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abq4581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6941: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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