Abstract
Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates. We perform whole-genome bisulfite sequencing to generate the first genome-wide methylation profiles of a cartilaginous fish, the elephant shark Callorhinchus milii. Employing these to determine the elephant shark methylome structure and its relationship with expression, we compare this with higher vertebrates and an invertebrate chordate using published methylation and transcriptome data. Results:Like higher vertebrates, the majority of elephant shark CG sites are highly methylated, and methylation is abundant across the genome rather than patterned in the mosaic configuration of invertebrates. This global hypermethylation includes transposable elements and the bodies of genes at all expression levels. Significantly, we document an inverse relationship between TSS methylation and expression in the elephant shark, supporting the presence of the repressive regulatory architecture shared by higher vertebrates. Our demonstration that methylation patterns in a cartilaginous fish are characteristic of higher vertebrates imply the conservation of this epigenetic modification system across jawed vertebrates separated by 465 million years of evolution. In addition, these findings position the elephant shark as a valuable model to explore the evolutionary history and function of vertebrate methylation.
Highlights
The methylation of DNA at cytosine bases constitutes an epigenetic regulatory system that is essential for the development of bony vertebrates[1,2,3]
Methylation of CG dinucleotides forms a heritable but flexible epigenetic memory that constitutes a critical regulatory system in bony vertebrates, where it is employed in the modulation of gene expression and suppression of transposon element activity
These features are not found in the sparsely methylated genomes of invertebrates, including chordates closely related to vertebrates[14,33,34,35,36,37,38,39,40], but establishing when this important regulatory system arose and the factors that drove its development has been has been impeded by a lack of methylation data from basal vertebrates (Figure 1)
Summary
The methylation of DNA at cytosine bases constitutes an epigenetic regulatory system that is essential for the development of bony vertebrates[1,2,3]. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates. Results: Like higher vertebrates, the majority of elephant shark CG sites are highly methylated, and methylation is abundant across the genome rather than patterned in the mosaic configuration of invertebrates This global hypermethylation includes transposable elements and the bodies of genes at all expression levels. These findings position the elephant shark as a valuable model to explore the evolutionary history and function of vertebrate methylation
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