Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: the Lyon repeat hypothesis.
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.
Bailey
J A
JA
Department of Genetics and Center for Human Genetics, Case Western Reserve School of Medicine and University Hospitals of Cleveland, Cleveland, OH, 44106, USA.
Carrel
L
L
Chakravarti
A
A
Eichler
E E
EE
D020029:Base Pairing; D005260:Female; D006801:Humans; D005810:Multigene Family; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome