Authors
Jose de Los Rios Barreda, Maria E Ferreiro, Natasha Jansz, Charles C Bell, Juan M Botto, Trung V Nguyen, Barun Pradhan, Minchun Chen, Ana Colomer-Boronat, Darwin J Da Costa Guevara, Diane A Flasch, Sabrina Gericke, Thomas E Wilson, Adam D Ewing, Sara R Heras, Francisco J Sanchez-Luque, Ryan Lister, John V Moran, Geoffrey J Faulkner
Published in
Science (New York, N.Y.). Volume 393. Issue 6810. Pages eadz8081. Jul 30, 2026. Epub Jul 30, 2026.
Abstract
X-chromosome inactivation (XCI) enables gene dosage compensation in XX eutherians. Long interspersed element-1 (LINE-1 or L1) retrotransposons are unusually abundant on the human X chromosome and are hypothesized to facilitate XCI. Here, we used long-read DNA sequencing to conduct a haplotype-aware analysis of engineered L1 integration preferences in the PA-1 human embryonic carcinoma cell line. Crucially, clonal XCI in PA-1 cells enabled derivation of active (Xa) and inactive (Xi) X-chromosome haplotypes. L1 integration strongly favored the Xi and other genomic regions that undergo DNA replication late in S-phase. These results suggest that the X chromosome is L1 rich because of XCI and imply that L1 integration preference for the Xi in XX individuals could potentially double the frequency of X-linked pathogenic L1 mutations in their XY descendants.
PMID:
42531392
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.
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