Abstract
The chemical modification of DNA bases plays a key role in epigenetic gene regulation. While much attention has been focused on the classical epigenetic mark, 5-methylcytosine, the field garnered increased interest through the recent discovery of additional modifications. In this review, we focus on the epigenetic regulatory roles of DNA modifications in animals. We present the symmetric modification of 5-methylcytosine on CpG dinucleotide as a key feature, because it permits the inheritance of methylation patterns through DNA replication. However, the distribution patterns of cytosine methylation are not conserved in animals and independent molecular functions will likely be identified. Furthermore, the discovery of enzymes that catalyse the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine not only identified an active demethylation pathway, but also a candidate for a new epigenetic mark associated with activated transcription. Most recently, N6-methyladenine was described as an additional eukaryotic DNA modification with epigenetic regulatory potential. Interestingly, this modification is also present in genomes that lack canonical cytosine methylation patterns, suggesting independent functions. This newfound diversity of DNA modifications and their potential for combinatorial interactions indicates that the epigenetic DNA code is substantially more complex than previously thought.
Highlights
To establish and maintain cellular identity during development, specific memory mechanisms have evolved that regulate gene expression patterns epigenetically
Central to this is the concept of epigenetic marks, specific DNA or chromatin modifications that can be inherited through cell divisions
Epigenetic DNA modifications generally affect the accessibility of genomic regions for regulatory proteins or protein complexes, for example by preventing interactions or by recruiting specific readers
Summary
To establish and maintain cellular identity during development, specific memory mechanisms have evolved that regulate gene expression patterns epigenetically. More than 80% of the CpG dinucleotides are methylated, Figure 1 DNA modifications with epigenetic regulatory functions and their interdependencies.
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