Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: The Lyon repeat hypothesis
- Department of Genetics and Center for Human Genetics, Case Western Reserve School of Medicine and University Hospitals of Cleveland, Cleveland, OH, 44106
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Edited by Stanley M. Gartler, University of Washington, Seattle, WA, and approved April 3, 2000 (received for review February 15, 2000)
Abstract
X inactivation is a chromosome-specific form of genetic regulation in which thousands of genes on one homologue become silenced early in female embryogenesis. Although many aspects of X inactivation are now understood, the spread of the X inactivation signal along the entire length of the chromosome remains enigmatic. Extending the Gartler–Riggs model [Gartler, S. M. & Riggs, A. D. (1983) Annu. Rev. Genet. 17, 155–190], Lyon recently proposed [Lyon, M. F. (1998) Cytogenet. Cell Genet. 80, 133–137] that a nonrandom organization of long interspersed element (LINE) repetitive sequences on the X chromosome might be responsible for its facultative heterochromatization. In this paper, we present data indicating that the LINE-1 (L1) composition of the human X chromosome is fundamentally distinct from that of human autosomes. The X chromosome is enriched 2-fold for L1 repetitive elements, with the greatest enrichment observed for a restricted subset of LINE-1 elements that were active <100 million years ago. Regional analysis of the X chromosome reveals that the most significant clustering of these elements is in Xq13–Xq21 (the center of X inactivation). Genomic segments harboring genes that escape inactivation are significantly reduced in L1 content compared with X chromosome segments containing genes subject to X inactivation, providing further support for the association between X inactivation and L1 content. These nonrandom properties of L1 distribution on the X chromosome provide strong evidence that L1 elements may serve as DNA signals to propagate X inactivation along the chromosome.
Footnotes
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↵ * To whom reprint requests should be addressed at: Department of Genetics, Case Western Reserve University, BRB720, 10900 Euclid Ave., Cleveland, OH 44106. E-mail: eee{at}po.cwru.edu.
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This paper was submitted directly (Track II) to the PNAS office.
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See commentary on page 6248.
- Abbreviations:
- LINE,
- long interspersed element;
- L1,
- LINE-1
- Copyright © 2000, The National Academy of Sciences
