DNA Methylation: Shared and Divergent Features across Eukaryotes

Abstract

Chemical modification of nucleotide bases in DNA provides one mechanism for conveying information in addition to the genetic code. 5-methylcytosine (5mC) represents the most common chemically modified base in eukaryotic genomes. Sometimes referred to simply as DNA methylation, in eukaryotes 5mC is most prevalent at CpG dinucleotides and is frequently associated with transcriptional repression of transposable elements. However, 5mC levels and distributions are variable across phylogenies, and emerging evidence suggests that the functions of DNA methylation may be more diverse and complex than was previously appreciated. We summarize the current understanding of DNA methylation profiles and functions in different eukaryotic lineages.

Keywords: 5-methylcytosine; DNA methylation; DNA methyltransferases; DNMT; gene body DNA methylation; genome integrity; genomic imprinting; heterochromatin.

Figure 1.. Schematic diagram of de novo and maintenance DNA methylation.

Methylation of cytosines de novo is independent of existing 5mC and can be targeted to cytosines in CpG and non-CpG contexts. Recruitment of de novo cytosine methyltransferases is regulated by small RNAs and/or specific chromatin modifications. Maintenance methylation involves recognition of hemi-methylated CpG sites generated during DNA replication. Maintenance methyltransferases target CpG sequences on the newly synthesized strand to generate a fully methylated CpG site.

Figure 2:. Evolutionary relationship of eukaryotic DNA methyltransferases.

DNMT1 homologs are found in essentially all eukaryotes that utilize 5mC, whereas lineage-specific losses and gains of DNA methyltransferases are found in specific taxa. This phylogeny is a representation and is not applicable to all species within each lineage due to the recurrent loss of DNA methylation machinery. Figure courtesy of Adam Bewick.