DNA methylation marks inter-nucleosome linker regions throughout the human genome

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1 USC Epigenome Center, University of Southern California, Los Angeles, CA, United States
2 Division of Bioinformatics, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, United States
3 USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States
4 Graduate Program in Genetic, Molecular and Cellular Biology, University of Southern California, Los Angeles, CA, United States
DOI
10.7287/peerj.preprints.27v1
Published
Accepted
Subject Areas
Bioinformatics, Genomics, Molecular Biology
Keywords
DNA methylation, nucleosome positioning, chromatin, CTCF, next-generation sequencing, MNase, epigenetics, Partially Methylated Domains, nucleosomal arrays
Copyright
© 2013 Berman et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cite this article
Berman BP, Liu Y, Kelly TK. 2013. DNA methylation marks inter-nucleosome linker regions throughout the human genome. PeerJ PrePrints 1:e27v1

Abstract

Nucleosome organization and DNA methylation are two epigenetic mechanisms that are important for proper control of mammalian transcription. Numerous lines of evidence suggest an interaction between these two mechanisms, but the nature of this interaction in vivo remains elusive. Whole-genome DNA methylation sequencing studies have shown that human methylation levels are periodic at intervals of approximately 190 bp, suggesting a genome-wide relationship between the two marks. A recent report (Chodavarapu et al., 2010) attributed this to higher methylation levels of DNA within nucleosomes. Here, we propose an alternate explanation for these nucleosomal periodicities. By examining methylation patterns in published datasets, we find that genome-wide methylation levels are highest within the linker regions that occur between nucleosomes in multi-nucleosome arrays. This effect is most prominent within long-range Partially Methylated Domains (PMDs) and the strongly positioned nucleosomes that flank CTCF binding sites. The CTCF-flanking nucleosomes retain positioning even in regions completely devoid of CpG dinucleotides, suggesting that DNA methylation is not required for proper positioning. We propose that DNA methylation is inhibited by histone proteins at CTCF and other unknown classes of nucleosomes within PMDs.