The conserved functional role of non-CpG methylation in mammalian and avian brain

K.M. Schachtschneider, O. Madsen, V.N. Laine, M.F.L. Derks, L.B. Schook, M.A.M. Groenen, K.J.F. Verhoeven, K. van Oers
Plant and Animal Genome XXIV Conference, January 9-13, 2016, San Diego, CA

DNA methylation is an epigenetic regulator of gene expression that plays a role in many cellular processes affecting a variety of traits. In this study DNA methylation was assessed in neuronal tissue from three pigs (frontal lobe) and one great tit (whole brain) using reduced representation and whole genome bisulfite sequencing, respectively. In addition, gene transcription patterns were profiled using RNA-seq. In total over 1.5 and 10.2 million CpG, and 5.5 and 167.4 million non-CpG sites were covered in the porcine and great tit samples, respectively. The observed genome-wide DNA methylation patterns in both species were consistent with previous mammalian findings, including low but significant non-CpG methylation that occurred predominantly at CpA dinucleotides. Both CpG and non-CpG methylation were negatively correlated with gene expression in porcine (Spearman’s rho < -0.053, P < 1x10-15) and great tit brain (Spearman’s rho < -0.22, P < 0.0001). In addition, increased CpG and decreased non-CpG methylation was found within transposable elements (TEs) compared to surrounding regions in the great tit brain. TE activity was negatively correlated with non-CpG methylation both within TEs (Spearman’s rho -0.12, P < 1x10-15) and the surrounding 2 kb regions (Spearman’s rho < -0.19, P < 1x10-15). These findings provide the first evidence for conservation of non-CpG methylation in mammalian and avian neuronal tissue, and suggest a functional role for non-CpG methylation in avian neuronal tissue. These results raise interesting questions regarding the universal role of non-CpG methylation in neuronal epigenetic regulation and its potential role in learning and memory.