Conserved and divergent patterns of DNA methylation in higher vertebrates.
Bottom Line: DNA methylation in the genome plays a fundamental role in the regulation of gene expression and is widespread in the genome of eukaryotic species.For example, in higher vertebrates, there is a "global" methylation pattern involving complete methylation of CpG sites genome-wide, except in promoter regions that are typically enriched for CpG dinucleotides, or so called "CpG islands." Here, we comprehensively examined and compared the distribution of CpG sites within ten model eukaryotic species and linked the observed patterns to the role of DNA methylation in controlling gene transcription.Comparative analysis with four other higher vertebrates revealed that the primary regulatory role of the DNA methylation system is highly conserved in higher vertebrates.
Affiliation: Department of Biostatistics & Computational Biology, SKLG, School of Life Sciences, Fudan University, Shanghai, China School of Biosciences, The University of Birmingham, Birmingham B15 2TT United Kingdom.Show MeSH
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Mentions: To further characterize the nonrandom distribution of CpGs in higher vertebrate promoters, we looked at the occurrence of “CpG islands,” which are recognized as small dispersed regions of DNA sequence that contain highly dense clusters of CpG dinucleotides relative to the whole genome. The widely accepted definition of a CpG island is a genomic region at least 200 bp in length, with GC content fraction >50% and an observed/expected CpG percentage ratio of >60% (Gardiner-Gardner and Frommer 1987). Among the 34,257 annotated promoters of the human genome, we found 21,890 (63.9%) promoters containing CpG islands, whereas the other 12,367 (36.1%) have only few CpG dinucleotides. For the other five higher vertebrate species, CpG islands were detected in over half of their annotated promoters. The density of CpG sites in the promoters of all six higher vertebrates showed a bimodal distribution (fig. 2), which was reported previously only in the human genome (Saxonov et al. 2006; Glass 2007). In contrast, no CpG islands were found in the four lower vertebrate, invertebrate, or plant genomes, and a unimodal distribution of CpG sites was observed (fig. 2). This difference cannot be attributed to the difference in the GC content distribution between the two groups because the distribution does not clearly differ between the two groups (supplementary fig. S1, Supplementary Material online). We proceeded to explore the functional roles of DNA methylation in regulating gene expression and attempted to explain the bimodal distribution pattern of CpGs in the promoters of higher vertebrates.Fig. 2.—
Affiliation: Department of Biostatistics & Computational Biology, SKLG, School of Life Sciences, Fudan University, Shanghai, China School of Biosciences, The University of Birmingham, Birmingham B15 2TT United Kingdom.