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Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages

Author

Listed:
  • Stefan Schoenfelder

    (Babraham Institute
    Babraham Institute)

  • Borbala Mifsud

    (QMUL
    Education City)

  • Claire E. Senner

    (Babraham Institute
    University of Cambridge)

  • Christopher D. Todd

    (QMUL)

  • Stephanie Chrysanthou

    (Babraham Institute)

  • Elodie Darbo

    (Bordeaux Bioinformatics Center
    INSERM ACTION U1218, Institut Bergonié)

  • Myriam Hemberger

    (Babraham Institute
    University of Cambridge)

  • Miguel R. Branco

    (QMUL)

Abstract

The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer–gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions.

Suggested Citation

  • Stefan Schoenfelder & Borbala Mifsud & Claire E. Senner & Christopher D. Todd & Stephanie Chrysanthou & Elodie Darbo & Myriam Hemberger & Miguel R. Branco, 2018. "Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06666-4
    DOI: 10.1038/s41467-018-06666-4
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    Cited by:

    1. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Kaela M. Varberg & Esteban M. Dominguez & Boryana Koseva & Joseph M. Varberg & Ross P. McNally & Ayelen Moreno-Irusta & Emily R. Wesley & Khursheed Iqbal & Warren A. Cheung & Carl Schwendinger-Schreck, 2023. "Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    3. William Villiers & Audrey Kelly & Xiaohan He & James Kaufman-Cook & Abdurrahman Elbasir & Halima Bensmail & Paul Lavender & Richard Dillon & Borbála Mifsud & Cameron S. Osborne, 2023. "Multi-omics and machine learning reveal context-specific gene regulatory activities of PML::RARA in acute promyelocytic leukemia," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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