Tissue-specific DNA methylation is conserved across species and driven by primary sequence conservation

Tissue specific differentially methylated regions (DMRs) have been shown to play important roles in tissue specification, but little is known about the conservation pattern of genome-wide DNA methylation distribution that encodes tissue specifity. Using a comparative approach, we identified and compared the tissue-specific DNA methylation patterns of the rat against that of mouse and human across three common tissue types. We found that 10%-40% of this tissue-specific DNA methylation pattern is conserved, and this epigenetic onservation is associated with the conservation of tissue specific TFBS. To evaluate the epigenetic evolution of tissue specific DMRs, we generated complete DNA methylome maps for rat blood, brain, sperm, and mouse blood by integrating data from methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq). We have also profiled DNA methylation datasets for mouse brain, sperm, and human blood, brain, sperm, as well as ChIP-seq data in the matching tissue types. These data were collected from the Human Epigenome Roadmap and MouseENCODE consortia; Mouse Brain: GSE53694 [GSM1299110, GSM1299111] Mouse Sperm: GSE49623 [GSM1202750-GSM1202753] Human Blood: GSE16368 [GSM543023] Human Brain: SRP002318 Human Sperm: GSE30340 [GSM752295, GSM752296]