Nucleotide distance influences co-methylation between nearby CpG sites.


Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) "Gaetano Salvatore", Consiglio Nazionale delle Ricerche (CNR), Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Via S. Pansini 5, 80131 Naples, Italy. Electronic address: [Email]


The tendency of individual CpG sites to be methylated is distinctive, non-random and well-regulated throughout the genome. We investigated the structural and spatial factors influencing CpGs methylation by performing an ultra-deep targeted methylation analysis on human, mouse and zebrafish genes. We found that methylation is not a random process and that closer neighboring CpG sites are more likely to share the same methylation status. Moreover, if the distance between CpGs increases, the degree of co-methylation decreases. We set up a simulation model to analyze the contribution of both the intrinsic susceptibility and the distance effect on the probability of a CpG to be methylated. Our finding suggests that the establishment of a specific methylation pattern follows a universal rule that must take into account of the synergistic and dynamic interplay of these two main factors: the intrinsic methylation susceptibility of specific CpG and the nucleotide distance between two CpG sites.


Co-methylation,DNA methylation,Intrinsic methylation susceptibility,Nearby CpG sites,Nucleotide distance effect,