Base-resolution analyses of parent-of-origin and sequence dependent allele specific DNA methylation in the mouse genome (ChIP-seq and Methyl-seq)

Allele specific DNA methylation (ASM) is crucial for genomic imprinting and mammalian development. Here we present a base-resolution, genome-wide allelic DNA methylation map for both CG and non-CG sites in the mouse brain. We found parent-of-origin dependent (imprinted) ASM at 1,952 CGs which form 55 discrete clusters. This uncovers 31 reported differentially methylated regions (DMRs), including virtually all known germline DMRs, and 24 novel candidate DMRs with some occurring at microRNA genes. In the same adult tissue we also report a surprising presence of non-CG methylation with some showing evidence of imprinting. Finally, we identified sequence dependent ASM at 131,765 CGs. Interestingly, methylation at these sites exhibits a strong dependence on the immediate adjacent bases, allowing us to define a conserved sequence preference for the mammalian DNA methylation machinery. Our genome-wide ASM map should help with understanding the epigenetic differences between two parental genomes in mammals.