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Enhancer rewiring in tumors: an opportunity for therapeutic intervention

Oncogene volume 40, pages 3475–3491 (2021)Cite this article

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Abstract

Enhancers are cis-regulatory sequences that fine-tune expression of their target genes in a spatiotemporal manner. They are recognized by sequence-specific transcription factors, which in turn recruit transcriptional coactivators that facilitate transcription by promoting assembly and activation of the basal transcriptional machinery. Their functional importance is underscored by the fact that they are often the target of genetic and nongenetic events in human disease that disrupt their sequence, interactome, activation potential, and/or chromatin environment. Dysregulation of transcription and addiction to transcriptional effectors that interact with and modulate enhancer activity are common features of cancer cells and are amenable to therapeutic intervention. Here, we discuss the current knowledge on enhancer biology, the broad spectrum of mechanisms that lead to their malfunction in tumor cells, and recent progress in developing drugs that efficaciously target their dependencies.

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Fig. 1: Distal regulation of promoter activity by enhancers.

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Acknowledgements

Work in the lab of RM is supported by the Fondation pour la Recherche Médicale (Equipe FRM EQU202003010312). LR work was partly supported by a research grant from Pfizer. We thank Daniel Holoch and Ming-Kang Lee for their critical review of the manuscript.

Author information

Authors and Affiliations

  1. Institut Curie, Paris Sciences et Lettres Research University, Paris, France

    Laia Richart & Raphaël Margueron

  2. INSERM U934/CNRS UMR3215, Paris, France

    Laia Richart & Raphaël Margueron

  3. Department of Medical Oncology, Institut Curie, Saint-Cloud, Paris, France

    François-Clément Bidard

  4. Circulating Tumor Biomarkers Laboratory, SIRIC2 Institut Curie, Paris, France

    François-Clément Bidard

  5. UVSQ, Université Paris-Saclay, Saint-Cloud, Paris, France

    François-Clément Bidard

Authors
  1. Laia Richart
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  2. François-Clément Bidard
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  3. Raphaël Margueron
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Corresponding author

Correspondence to Raphaël Margueron.

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Richart, L., Bidard, FC. & Margueron, R. Enhancer rewiring in tumors: an opportunity for therapeutic intervention. Oncogene 40, 3475–3491 (2021). https://doi.org/10.1038/s41388-021-01793-7

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