Conservation And Divergence Of DNA Methylationpatterns Among Multiple Tissues/cells In Human And Mouse

DNA methylation has been regarded as essential epigenetic mechanism involved in gene expression in specific spatiotemporal pattern.Genome-wide CpG islands (CGIs) and gene promoter regions methylation profiles have been described in numbers of tissues and cells among different species. However, the inter-tissues and inter-species DNA methylation pattern and function in other genome regions are not yet clear. To this end, we systematically analyzed the methylation difference in genome-wide CpG-sites location within seven genome categories (Up2kb,5’-UTR, CodingExon, Intron,3’-UTR, Down2kb and Intergenic regions) across multiple tissues in human and mouse.We collected methylation data in the human and mouse ES cells, B cells, fibroblast, brain, liver and lung samples detected by RRBS provided by Meissner A et al. QDMR, a bioinformatic tool based on Shannon entropy, was utilized to quantify and identify methylation differences across these tissues and cells in both species. Further, we analyzed the functions of genes related with methylation differences within seven genome region categories by functional annotation tools in the DAVID Bioinformatics Resources6.7website.We found that most CpG-sites located in CGIs, Up2kb,5’-UTR and Intron regions in the both species are hypomethylated. The Person Correlation Coefficient (PCC) analysis exhibited that genome-wild DNA methylation profile is significantly conserved across6different tissues and cells from the same species (0.806<PCC<0.912, p<10-16). Next, we analyzed the DNA methylation patterns in homologous genes between human and mouse. For the same tissue/cell, DNA methylation is significantly conservative between human and mouse in3’-UTR and Down2kb (0.543<PCC<0.838, P<10-5), while it is not in5’-UTR. It is interesting that methylation entropy among human tissues/cells and that among mouse tissues/cells is positively correlated with each other, which indicated that the methylation variability in homologous genes is also conservative in both species. Notably, two-dimensional cluster PPC analysis revealed that the inter-tissues DNA methylation patterns are more conservative relative to inter-species in all of the genome seven categories. Furthermore, the homologous genes related to tissue-specific differentially methylated CpG sites identified by QDMR in each of seven genome categories are involved in similar biological processes in human and mouse. Taken together, we provided new insights into conservation and divergence of genome-wide DNA methylation patterns within seven genome categories across multiple tissues and cells in human and mouse.