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Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression

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  • Lin Li-Bao

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Centro Andaluz de Biología del Desarrollo (CABD))

  • Covadonga Díaz-Díaz

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV))

  • Morena Raiola

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Rocío Sierra

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV))

  • Susana Temiño

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV))

  • Francisco J. Moya

    (Centro Nacional de Investigaciones Oncológicas (CNIO))

  • Sandra Rodriguez-Perales

    (Centro Nacional de Investigaciones Oncológicas (CNIO))

  • Elisa Santos

    (CNIC)

  • Giovanna Giovinazzo

    (Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
    CNIC)

  • Tore Bleckwehl

    (University of Cologne
    RWTH Aachen University)

  • Álvaro Rada-Iglesias

    (CSIC/University of Cantabria)

  • Francois Spitz

    (The University of Chicago
    European Molecular Biology Laboratory)

  • Miguel Torres

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV))

Abstract

MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.

Suggested Citation

  • Lin Li-Bao & Covadonga Díaz-Díaz & Morena Raiola & Rocío Sierra & Susana Temiño & Francisco J. Moya & Sandra Rodriguez-Perales & Elisa Santos & Giovanna Giovinazzo & Tore Bleckwehl & Álvaro Rada-Igles, 2024. "Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48258-5
    DOI: 10.1038/s41467-024-48258-5
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    References listed on IDEAS

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    1. Cristina Clavería & Giovanna Giovinazzo & Rocío Sierra & Miguel Torres, 2013. "Myc-driven endogenous cell competition in the early mammalian embryo," Nature, Nature, vol. 500(7460), pages 39-44, August.
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