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Dynamic dosage changes in X-linked transposable elements during mammalian dosage compensation

Author

Listed:
  • Chunyao Wei

    (Massachusetts General Hospital
    Harvard Medical School)

  • Barry Kesner

    (Massachusetts General Hospital
    Harvard Medical School)

  • Uri Weissbein

    (Massachusetts General Hospital
    Harvard Medical School)

  • Peera Wasserzug-Pash

    (Massachusetts General Hospital
    Harvard Medical School)

  • Priyojit Das

    (Massachusetts General Hospital
    Harvard Medical School)

  • Jeannie T. Lee

    (Massachusetts General Hospital
    Harvard Medical School)

Abstract

In mammals, X-linked dosage compensation involves X-chromosome inactivation to balance X chromosome dosage between males and females, and hyperactivation of the remaining X-chromosome (Xa-hyperactivation) to achieve X-autosome balance in both sexes. Studies of both processes have largely focused on coding genes and have not accounted for transposable elements which comprise 50% of the X-chromosome with numerous epigenetic functions. Here we develop a new bioinformatic pipeline tailored to repetitive elements with capability for allelic discrimination. We then apply the pipeline to our recent So-Smart-Seq analysis of single embryos to comprehensively interrogate whether X-linked transposable elements are subject to either X-chromosome inactivation or Xa-hyperactivation. We observe significant differences in repeat silencing in parentally driven “imprinted” versus zygotically driven “random” X-chromosome inactivation. Chromosomal positioning, genetic background and evolutionary age impact their silencing. In contrast, transposable elements do not undergo Xa-hyperactivation. Evolutionary and functional implications are discussed.

Suggested Citation

  • Chunyao Wei & Barry Kesner & Uri Weissbein & Peera Wasserzug-Pash & Priyojit Das & Jeannie T. Lee, 2025. "Dynamic dosage changes in X-linked transposable elements during mammalian dosage compensation," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64865-2
    DOI: 10.1038/s41467-025-64865-2
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    References listed on IDEAS

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