Contribution Of Genetic Variation And Developmental Stage To Methylome Dynamics In Myeloid Differentiation

Abstract

DNA methylation is important to establish a cells developmental identity. It also modulates cellular responses to endogenous developmental stimuli or environmental changes. We designed an in vitro myeloid differentiation model to analyze the genetic and developmental contribution to methylome dynamics using whole-genome bisulfide sequencing and transcriptome sequencing. Using a recursive partitioning approach, we identified 34,502 differentially methylated regions (DMRs) associated with genetic background and/or developmental stimuli. Specifically, 23,792 DMRs (69%) were significantly associated with inter-individual variations, of which 82% were associated with genetic polymorphisms in cis. Notably, inter-individual variations further modified 57 of 212 (26%) developmental DMRs with transcriptomic responses. Our study presents a novel analytical approach to determine the bona fide genetic contribution embedded in outlier patterns of CpG-SNPs in individual methylomes. This approach can be used to study genetic and epigenetic mechanisms underlying differential responses to developmental stimuli, environmental changes, and inter-individual differences in drug responses.