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Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape

Author

Listed:
  • John E. Froberg

    (Massachusetts General Hospital
    Harvard Medical School
    Howard Hughes Medical Institute)

  • Stefan F. Pinter

    (Massachusetts General Hospital
    Harvard Medical School
    Howard Hughes Medical Institute
    University of Connecticut Health Center)

  • Andrea J. Kriz

    (Massachusetts General Hospital
    Harvard Medical School
    Howard Hughes Medical Institute)

  • Teddy Jégu

    (Massachusetts General Hospital
    Harvard Medical School
    Howard Hughes Medical Institute)

  • Jeannie T. Lee

    (Massachusetts General Hospital
    Harvard Medical School
    Howard Hughes Medical Institute)

Abstract

The mammalian inactive X-chromosome (Xi) is structurally distinct from all other chromosomes and serves as a model for how the 3D genome is organized. The Xi shows weakened topologically associated domains and is instead organized into megadomains and superloops directed by the noncoding loci, Dxz4 and Firre. Their functional significance is presently unclear, though one study suggests that they permit Xi genes to escape silencing. Here, we find that megadomains do not precede Xist expression or Xi gene silencing. Deleting Dxz4 disrupts the sharp megadomain border, whereas deleting Firre weakens intra-megadomain interactions. However, deleting Dxz4 and/or Firre has no impact on Xi silencing and gene escape. Nor does it affect Xi nuclear localization, stability, or H3K27 methylation. Additionally, ectopic integration of Dxz4 and Xist is not sufficient to form megadomains on autosomes. We conclude that Dxz4 and megadomains are dispensable for Xi silencing and escape from X-inactivation.

Suggested Citation

  • John E. Froberg & Stefan F. Pinter & Andrea J. Kriz & Teddy Jégu & Jeannie T. Lee, 2018. "Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape," Nature Communications, Nature, vol. 9(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07446-w
    DOI: 10.1038/s41467-018-07446-w
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    Cited by:

    1. Antonio Lentini & Huaitao Cheng & J. C. Noble & Natali Papanicolaou & Christos Coucoravas & Nathanael Andrews & Qiaolin Deng & Martin Enge & Björn Reinius, 2022. "Elastic dosage compensation by X-chromosome upregulation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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