Abstract
BackgroundStudies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNA methylation in relation to gene expression. However, it is not well known how tissue-specific methylation varies between different functional and structural components of genes and genomes. Using whole-genome bisulfite sequencing data we here describe both CpG and non-CpG methylation profiles of whole blood and brain tissue in relation to gene features, CpG-islands (CGIs), transposable elements (TE), and their functional roles in an ecological model species, the great tit (Parus major).ResultsWe show that hypomethylation at the transcription start site (TSS) is enriched in genes with functional classes that relate directly to processes specific to each tissue type. We find that 6877 (~21 %) of the CGIs are differentially methylated between blood and brain, of which 1186 and 2055 are annotated to promoter and intragenic regions, respectively. We observe that CGI methylation in promoter regions is more conserved between tissues compared to CGI methylation in intra and inter-genic regions. Differentially methylated CGIs in promoter and intragenic regions are overrepresented in genomic loci linked to development, suggesting a distinct role for CGI methylation in regulating expression during development. Additionally, we find significant non-CpG methylation in brain but not in blood with a strong preference for methylation at CpA dinucleotide sites. Finally, CpG hypermethylation of TEs is significantly stronger in brain compared to blood, but does not correlate with TE activity. Surprisingly, TEs showed significant hypomethylation in non-CpG contexts which was negatively correlated with TE expression.ConclusionThe discovery that TSS methylation levels are directly linked to functional classes related to each tissue provides new insights in the regulatory role of DNA-methylation patterns. The dominant sequence motifs for brain non-CpG methylation, similar to those found in mammals, suggests that a conserved non-CpG regulatory mechanism was already present in the amniote ancestor. The negative correlation between brain non-CpG methylation and TE activity (not found for CpG methylation) suggests that non-CpG is the dominant regulatory form of methylation in TE silencing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2653-y) contains supplementary material, which is available to authorized users.
Highlights
Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNA methylation in relation to gene expression
We found that genes associated with hypermethylated CGIs in brain compared to blood are largely involved in developmental processes
Our observation that non-CpG methylation negatively correlates with transposable elements (TE) activity suggests a distinct role for non-CpG methylation in TE silencing in the brain
Summary
Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNA methylation in relation to gene expression. DNA methylation is the addition of a methyl (-CH3) group to the 5’ carbon site of cytosines catalyzed by DNA-methyltransferases, which occurs mainly at CpG sites in animals [1]. It is involved in many biological processes including modulation of gene expression. The majority of methylation studies have been conducted on either humans or model species for human diseases, and studies on ecological model systems are rare Studies on such systems, where reference genomes are often lacking, mainly use targeted methods such as MSAFLP or RRBS that rely heavily on assumptions from human and rodent studies and provide only limited functional insights [2]. Whole methylome information will give us detailed insight into processes related to gene expression, silencing and tissue specialization, and allows us to better predict what variation is important for answering ecologically relevant questions
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