Description: DNA methylation is related closely to sequence contexts and chromatin modifications; however, their potential differences in different genomic regions across cell types remain largely unexplored. We used publicly available genome-scale DNA methylation and histone modification profiles to study their relationships among different genomic regions in human embryonic stem cells (H1), H1-derived neuronal progenitor cultured cells (NPC), and foetal fibroblasts (IMR90) using the Random forests classifier. Histone modifications achieved high accuracy in modelling DNA methylation patterns on a genome scale in the three cell types. The inclusion of sequence features helped improve accuracy only in non-promoter regions of IMR90. Furthermore, the top six feature combinations obtained by mean decrease Gini were important indicators of different DNA methylation patterns, suggesting that H3K4me2 and H3K4me3 are important indicators that are independent of genomic regions and cell types. H3K9me3 was IMR90-specific and exhibited a genomic region-specific correlation with DNA methylation. Variations of essential chromatin modification signals may effectively discriminate changes of DNA methylation between H1 and IMR90. Genes with different co-variations of epigenetic marks exhibited genomic region-specific biological relevance. This study provides an integrated strategy to identify systematically essential epigenetic and genetic elements of genomic region-specific and cell type-specific DNA methylation patterns. Scientific Reports 5 doi: 10.1038/srep08410