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Published online before print July 19, 2002, 10.1101/gr.74502
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Vol. 12, Issue 8, 1246-1256, August 2002

LETTER
CpG Methylation Modifies the Genetic Stability of Cloned Repeat Sequences

Kerrie Nichol,1 and and Christopher E. Pearson1,2,3

1 Program of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; 2 Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada

The genetic stability of tandemly repeated DNAs is affected by repeat sequence, tract length, tract purity, and replication direction. Alterations in DNA methylation status are thought to influence many processes of mutagenesis. By use of bacterial and primate cell systems, we have determined the effect of CpG methylation on the genetic stability of cloned di-, tri-, penta- and minisatellite repeated DNA sequences. Depending on the repeat sequence, methylation can significantly enhance or reduce its genetic stability. This effect was evident when repeat tracts were replicated from either direction. Unexpectedly, methylation of adjacent sequences altered the stability of contiguous repeat sequences void of methylatable sites. Of the seven repeat sequences investigated, methylation stabilized five, destabilized one, and had no effect on another. Thus, although methylation generally stabilized repeat tracts, its influence depended on the sequence of the repeat. The current results lend support to the notion that the biological consequences of CpG methylation may be affected through local alterations of DNA structure as well as through direct protein-DNA interactions. In vivo CpG methylation in bacteria may have technical applications for the isolation and stable propagation of DNA sequences that have been recalcitrant to isolation and/or analyses because of their extreme instability.

[Supplementary material available online at http://www.genome.org.]

3 Corresponding author.

12:1246-1256 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00
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