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

Abstract

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. HighlightsO_LIA comprehensive atlas of allele-specific methylation in primary human cell types C_LIO_LI325k genomic regions show a bimodal pattern of of hyper- and hypo-methylation of DNA C_LIO_LIAllele-specific methylation at 34k genomic regions C_LIO_LITissue-specific effects at known imprinting control regions (ICRs) C_LIO_LI100s of novel loci exhibiting parentally-imprinted methylation C_LIO_LIParentally-imprinting methylation is often cell-type-specific C_LI