Fidelity of the methylation pattern and its variation in the genome

The methylated or unmethylated status of a CpG site is copied faithfully from parental DNA to daughter DNA, and functions as a cellular memory. However, no information is available for the fidelity of methylation pattern in unmethylated CpG islands (CGIs) or its variation in the genome. Here, we det...

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Bibliographic Details
Published in:Genome research 2003-05, Vol.13 (5), p.868-874
Main Authors: Ushijima, Toshikazu, Watanabe, Naoko, Okochi, Eriko, Kaneda, Atsushi, Sugimura, Takashi, Miyamoto, Kazuaki
Format: Article
Language:English
Subjects:
Base Composition - genetics
Breast - chemistry
Breast - cytology
Breast - metabolism
Cell Line
CpG Islands - genetics
DNA - chemistry
DNA - genetics
DNA Methylation
Epithelial Cells - chemistry
Epithelial Cells - metabolism
Genes - genetics
Genetic Variation - genetics
Genome, Human
Genomic Imprinting - genetics
Humans
Letters
Models, Statistical
Promoter Regions, Genetic - genetics
Sequence Analysis, DNA - methods
Sequence Analysis, DNA - statistics & numerical data
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Summary:The methylated or unmethylated status of a CpG site is copied faithfully from parental DNA to daughter DNA, and functions as a cellular memory. However, no information is available for the fidelity of methylation pattern in unmethylated CpG islands (CGIs) or its variation in the genome. Here, we determined the methylation status of each CpG site on each DNA molecule obtained from clonal populations of normal human mammary epithelial cells. Methylation pattern error rates (MPERs) were calculated based upon the deviation from the methylation patterns that should be obtained if the cells had 100% fidelity in replicating the methylation pattern. Unmethylated CGIs in the promoter regions of five genes showed MPERs of 0.018-0.032 errors/site/21.6 generations, and the fidelity of methylation pattern was calculated as 99.85%-99.92%/site/generation. In contrast, unmethylated CGIs outside the promoter regions showed MPERs more than twice as high (P < 0.01). Methylated regions, including a CGI in the MAGE-A3 promoter and DMR of the H19 gene, showed much lower MPERs than unmethylated CGIs. These showed that errors in methylation pattern were mainly due to de novo methylations in unmethylated regions. The differential MPERs even among unmethylated CGIs indicated that a promoter-specific protection mechanism(s) from de novo methylation was present.
ISSN:1088-9051
1054-9803
1549-5469
DOI:10.1101/gr.969603