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CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression

Author

Listed:
  • Martin Franke

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • Elisa De la Calle-Mustienes

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • Ana Neto

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • María Almuedo-Castillo

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • Ibai Irastorza-Azcarate

    (Max-Delbrück Center for Molecular Medicine)

  • Rafael D. Acemel

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • Juan J. Tena

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • José M. Santos-Pereira

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

  • José L. Gómez-Skarmeta

    (Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide)

Abstract

Coordinated chromatin interactions between enhancers and promoters are critical for gene regulation. The architectural protein CTCF mediates chromatin looping and is enriched at the boundaries of topologically associating domains (TADs), which are sub-megabase chromatin structures. In vitro CTCF depletion leads to a loss of TADs but has only limited effects over gene expression, challenging the concept that CTCF-mediated chromatin structures are a fundamental requirement for gene regulation. However, how CTCF and a perturbed chromatin structure impacts gene expression during development remains poorly understood. Here we link the loss of CTCF and gene regulation during patterning and organogenesis in a ctcf knockout zebrafish model. CTCF absence leads to loss of chromatin structure and affects the expression of thousands of genes, including many developmental regulators. Our results demonstrate the essential role of CTCF in providing the structural context for enhancer-promoter interactions, thus regulating developmental genes.

Suggested Citation

  • Martin Franke & Elisa De la Calle-Mustienes & Ana Neto & María Almuedo-Castillo & Ibai Irastorza-Azcarate & Rafael D. Acemel & Juan J. Tena & José M. Santos-Pereira & José L. Gómez-Skarmeta, 2021. "CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25604-5
    DOI: 10.1038/s41467-021-25604-5
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    Cited by:

    1. Thais Ealo & Victor Sanchez-Gaya & Patricia Respuela & María Muñoz-San Martín & Elva Martin-Batista & Endika Haro & Alvaro Rada-Iglesias, 2024. "Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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