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ASHG 2010 Annual Meeting Plenary Session: "DNA Methylation and the Evolution of Gene Regulation in Primates"
Speaker: Athma A. Pai, University of Chicago
November 3, 2010 (Washington, DC)

DESCRIPTION: Modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. While methylation patterns have been described in many contexts within species (for example, across different tissues), the extent to which these signatures are conserved across species has not been well characterized. To this end, we assayed genome-wide DNA methylation patterns in six livers, six hearts, and six kidneys from multiple humans and chimpanzees, using tissue samples for which genome-wide gene expression data are also available. Using the multi-species gene expression and methylation data for over 7000 genes, we were able to study the evolution of gene regulation in the context of conservation or changes in DNA methylation patterns across tissues and species. Overall, we found that inter-tissue methylation patterns are largely conserved between humans and chimpanzees, and we confirmed that hyper-methylation is correlated with decreased gene expression levels regardless of tissues or species. We identified a large number of genes that show differences in expression levels between tissues or across species, which can be explained, at least in part, by corresponding differences in methylation patterns. In particular, we observed differences in spatial expression patterns between humans and chimpanzee, which are likely to be explained by differences in tissue-specific methylation patterns across the species. By focusing on hemi-methylated genes, we were also able to identify genes that may be imprinted in only one of the species, as well as genes that likely escape X inactivation only in human or chimpanzee females. Finally, by considering genome-wide patterns, we estimated that inter-species differences in methylation patterns might underlie 5-8% of differences in gene expression levels between human and chimpanzee.

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