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Regenerative Medicine

Super-enhancers: drivers of cells’ identities and cells’ debacles

    Mélanie Lavaud

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    ,
    Robel Tesfaye

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    Cancéropôle Grand-Ouest, Réseau Épigénétique, Medical School, Nantes, 44035, France

    EpiSAVMEN, Epigenetic consortium Pays de la Loire, France

    ,
    Léa Lassous

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    ,
    Bénédicte Brounais

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    ,
    Marc Baud'huin

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    ,
    Franck Verrecchia

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    ,
    François Lamoureux

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    ,
    Steven Georges

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    &
    Benjamin Ory

    *Author for correspondence:

    E-mail Address: benjamin.ory@univ-nantes.fr

    CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University & Angers University, Medical School, Nantes, 44035, France

    Cancéropôle Grand-Ouest, Réseau Épigénétique, Medical School, Nantes, 44035, France

    EpiSAVMEN, Epigenetic consortium Pays de la Loire, France

    Published Online:https://doi.org/10.2217/epi-2023-0409

    Precise spatiotemporal regulations of gene expression are essential for determining cells’ fates and functions. Enhancers are cis-acting DNA elements that act as periodic transcriptional thrusters and their activities are cell type specific. Clusters of enhancers, called super-enhancers, are more densely occupied by transcriptional activators than enhancers, driving stronger expression of their target genes, which have prominent roles in establishing and maintaining cellular identities. Here we review the current knowledge on the composition and structure of super-enhancers to understand how they robustly stimulate the expression of cellular identity genes. We also review their involvement in the development of various cell types and both noncancerous and cancerous disorders, implying the therapeutic interest of targeting them to fight against various diseases.

    Tweetable abstract

    Super-enhancers orchestrate expressions of genes that shape cells’ identity, whether this identity is physiological or malignant. This review is a compendium of current knowledge. #epigenetic #superenhancers #cellsidentity

    Papers of special note have been highlighted as: •• of considerable interest

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