Evolution of CpH methylation in vertebrate brains

ABSTRACT: The brain requires complex mechanisms of genome regulation to encode and store behavioural information. In mammals, DNA methylation deposited at non-CG dinucleotides characterises brain epigenomes. However, it is unclear to what extent this non-canonical form of DNA methylation is evolutionarily conserved. To test this we profile brain cytosine methylation across the major vertebrate lineages, amphioxus, honeybee and octopus, finding that non-CG methylation in adult brain methylomes is restricted to vertebrates. In vertebrates, the genomic patterns of non-CG do not recapitulate those of CG methylation, yet both patterns are deeply conserved. Whereas low levels of gene body CG methylation demarcate a set of developmental transcription factors across tissues and species, a distinct set of neurodevelopmental genes accumulate non-CG methylation in neural tissues. We further show that the establishment of this methylation context coincides with the origin of the “writer” of non-CG methylation, the methyltransferase DNMT3A, and the “reader”, the methyl-CpG binding protein 2 (MeCP2), fuelled by the ancestral whole genome duplication in vertebrates. Surprisingly, MeCP2 evolved in a stepwise process, from an ancestral MBD4 protein with a dual role in transcriptional regulation and DNA repair in chordates. In sum, we show how a novel neural epigenomic layer assembled at the root of vertebrates and gained new regulatory roles partly independent from CG methylation, which could have fostered the sophisticated cognitive repertoires found in the vertebrate lineage.

ORGANISM(S): Octopus bimaculoides Danio rerio Branchiostoma lanceolatum Callorhinchus milii Monodelphis domestica Apis mellifera Ornithorhynchus anatinus Gallus gallus Lethenteron camtschaticum

PROVIDER: GSE141609 | GEO | 2020/10/26

REPOSITORIES: GEO