Non-CG DNA methylation in animal genomes

Cytosine DNA methylation is widespread in animal genomes and occurs predominantly at CG dinucleotides (mCG). While the roles of mCG, such as in genomic imprinting and genome stability, are well established, non-CG DNA methylation (mCH) remains poorly understood. In most vertebrate tissues, roughly 80% of CGs are methylated, whereas mCH levels are generally low, typically ranging from 1% to 3%. In vertebrates, mCH is most prevalent in neural tissue, oocytes and embryonic stem cells and has been linked to neurodevelopmental disorders. Moreover, mCH appears to have a conserved role in regulating vertebrate neural genomes, and recent studies suggest that it has functions in the embryogenesis of teleost fish. Overall, mCH represents an intriguing emerging aspect of gene regulation with potential implications for cellular identity, repeat silencing and neural function. In this Review, we provide a critical overview of the patterning, mechanisms and functional implications of mCH in animals.