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

Chunyao Wei, Barry Kesner, Uri Weissbein, Peera Wasserzug-Pash, Priyojit Das and Jeannie T. Lee ()
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Chunyao Wei: Massachusetts General Hospital
Barry Kesner: Massachusetts General Hospital
Uri Weissbein: Massachusetts General Hospital
Peera Wasserzug-Pash: Massachusetts General Hospital
Priyojit Das: Massachusetts General Hospital
Jeannie T. Lee: Massachusetts General Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-64865-2

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