A population-epigenetic model to infer site-specific methylation rates from double-stranded DNA methylation patterns
- 12 April 2005
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 102 (16), 5802-5807
- https://doi.org/10.1073/pnas.0502036102
Abstract
Cytosine methylation is an epigenetic mechanism in eukaryotes that is often associated with stable transcriptional silencing, such as in X-chromosome inactivation and genomic imprinting. Aberrant methylation patterns occur in several inherited human diseases and in many cancers. To understand how methylated and unmethylated states of cytosine residues are transmitted during DNA replication, we develop a population-epigenetic model of DNA methylation dynamics. The model is informed by our observation that de novo methylation can occur on the daughter strand while leaving the opposing cytosine unmethylated, as revealed by the patterns of methylation on the two complementary strands of individual DNA molecules. Under our model, we can infer site-specific rates of both maintenance and de novo methylation, values that determine the fidelity of methylation inheritance, from double-stranded methylation data. This approach can be used for populations of cells obtained from individuals without the need for cell culture. We use our method to infer cytosine methylation rates at several sites within the promoter of the human gene FMR1.Keywords
This publication has 36 references indexed in Scilit:
- How Are Alkynes Scrambled?Science, 2005
- Hemimethylation and Non-CpG Methylation Levels in a Promoter Region of Human LINE-1 (L1) Repeated ElementsJournal of Biological Chemistry, 2005
- Processive Methylation of Hemimethylated CpG Sites by Mouse Dnmt1 DNA MethyltransferasePublished by Elsevier BV ,2005
- Building for EarthquakesScience, 2004
- Fidelity of the Methylation Pattern and Its Variation in the GenomeGenome Research, 2003
- DNA methylation patterns and epigenetic memoryGenes & Development, 2002
- The somatic replication of DNA methylationCell, 1981
- Use of restriction enzymes to study eukaryotic DNA methylationJournal of Molecular Biology, 1978
- X inactivation, differentiation, and DNA methylationCytogenetic and Genome Research, 1975
- An Investigation of the Restraints with Respect to Sample Size Commonly Imposed on the Use of the Chi-Square StatisticJournal of the American Statistical Association, 1971