Abstract
Author SummaryEpigenetic modifications such as addition of methyl groups to cytosine in DNA play a role in regulating gene expression. To better understand these processes, knowledge of the methylation status of all cytosine bases in the genome (the methylome) is required. DNA methylation can differ between the two gene copies (alleles) in each cell. Such allele-specific methylation (ASM) can be due to parental origin of the alleles (imprinting), X chromosome inactivation in females, and other as yet unknown mechanisms. This may significantly alter the expression profile arising from different allele combinations in different individuals. Using advanced sequencing technology, we have determined the methylome of human peripheral blood mononuclear cells (PBMC). Importantly, the PBMC were obtained from the same male Han Chinese individual whose complete genome had previously been determined. This allowed us, for the first time, to study genome-wide differences in ASM. Our analysis shows that ASM in PBMC is higher than can be accounted for by regions known to undergo parent-of-origin imprinting and frequently (>80%) correlates with allele-specific expression (ASE) of the corresponding gene. In addition, our data reveal a rich landscape of epigenomic variation for 20 genomic features, including regulatory, coding, and non-coding sequences, and provide a valuable resource for future studies. Our work further establishes whole-genome sequencing as an efficient method for methylome analysis.
Highlights
DNA methylation plays a vital role in genome dynamics
We have determined the methylome of human peripheral blood mononuclear cells (PBMC)
The PBMC were obtained from the same male Han Chinese individual whose complete genome had previously been determined
Summary
DNA methylation plays a vital role in genome dynamics. It predominantly occurs at cytosine guanine dinucleotide (CpG) sites in somatic cells [1] and at non-CpG cytosines in embryonic stem cells [2] and perhaps other cells as well. DNA methylation at any of these sites can vary and affect many biological processes that impact on human health and disease [3]. The emergence of the next-generation sequencing of bisulfite converted DNA represents an important advance in the field of DNA methylation analysis [4,5,6].
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