Different measures of “genome-wide” DNA methylation exhibit unique properties in placental and somatic tissues

Abstract

DNA methylation of CpGs located in two types of repetitive elements—LINE1 (L1) and Alu—is used to assess “global” changes in DNA methylation in studies of human disease and environmental exposure. L1 and Alu contribute close to 30% of all base pairs in the human genome and transposition of repetitive elements is repressed through DNA methylation. Few studies have investigated whether repetitive element DNA methylation is associated with DNA methylation at other genomic regions, or the biological and technical factors that influence potential associations. Here, we assess L1 and Alu DNA methylation by Pyrosequencing of consensus sequences and using subsets of probes included in the Illumina Infinium HumanMethylation27 BeadChip array. We show that evolutionary age and assay method affect the assessment of repetitive element DNA methylation. Additionally, we compare Pyrosequencing results for repetitive elements to average DNA methylation of CpG islands, as assessed by array probes classified into strong, weak and non-islands. We demonstrate that each of these dispersed sequences exhibits different patterns of tissue-specific DNA methylation. Correlation of DNA methylation suggests an association between L1 and weak CpG island DNA methylation in some of the tissues examined. We caution, however, that L1, Alu and CpG island DNA methylation are distinct measures of dispersed DNA methylation and one should not be used in lieu of another. Analysis of DNA methylation data is complex and assays may be influenced by environment and pathology in different or complementary ways.

Keywords: :

• Alu
• CpG island
• DNA Methylation
• L1
• epigenetics
• placenta
• repetitive elements

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Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors would like to thank Ruby Jiang for technical assistance, Courtney Hanna and Dr. Kirsten Hogg for their constructive comments, Lucia Lam and Sarah Neumann for aid in microarray processing and analysis, Dr. Angela Devlin for use of the Biotage PyroMark^TM MD machine, Dr. Dixie Mager for useful conversations and Katarzyna Stepien for her figure illustrations. This work was supported by funds from the BC Clinical Genomics Network, a grant from the Canadian Institute for Health Research to WPR, and a training fellowship from the Child and Family Research Institute to EMP. MSK is a Scholar of the Michael Smith Foundation for Health Research and the Canadian Institute for Advanced Research. Sources of support include BC Clinical Genomics Network, Canadian Institute for Health Research and the Child and Family Research Institute