Atlas of imprinted and allele-specific DNA methylation in the human body

Allele-specific DNA methylation, determined genetically or epigenetically, is involved in gene regulation and underlies multiple pathologies. Yet, our knowledge of this phenomenon is partial, and largely limited to blood lineages. Here, we present a comprehensive atlas of allele-specific DNA methylation, using deep whole-genome sequencing across 39 normal human cell types. We identified 325k genomic regions, covering 6% of the genome and containing 11% of all CpG sites, that show a bimodal distribution of methylated and unmethylated molecules. In 34K of these regions, genetic variations at individual alleles segregate with methylation patterns, thus validating allele-specific methylation. We also identified 460 regions showing parentally-imprinted methylation, the majority of which were not previously reported. Surprisingly, sequence-dependent and parent-dependent methylation patterns are often restricted to specific cell types, revealing unappreciated variation in the human allele-specific methylation across the human body. The atlas provides a resource for studying allele-specific methylation and regulatory mechanisms underlying imprinted expression in specific human cell types. Highlights A comprehensive atlas of allele-specific methylation in primary human cell types 325k genomic regions show a bimodal pattern of of hyper- and hypo-methylation of DNA Allele-specific methylation at 34k genomic regions Tissue-specific effects at known imprinting control regions (ICRs) 100s of novel loci exhibiting parentally-imprinted methylation Parentally-imprinting methylation is often cell-type-specific