The Effect of DNA CpG Methylation on the Dynamic Conformation of a Nucleosome

Abstract

DNA methylation is an important epigenetic mark that is known to induce chromatin condensation and gene silencing. We used a time-domain fluorescence lifetime measurement to quantify the effects of DNA hypermethylation on the conformation and dynamics of a nucleosome. Nucleosomes reconstituted on an unmethylated and a methylated DNA both exhibit dynamic conformations under physiological conditions. The DNA end breathing motion and the H2A-H2B dimer destabilization dominate the dynamic behavior of nucleosomes at low to medium ionic strength. Extensive DNA CpG methylation, surprisingly, does not help to restrain the DNA breathing motion, but facilitates the formation of a more open nucleosome conformation. The presence of the divalent cation, Mg2+, essential for chromatin compaction, and the methyl donor molecule SAM, required for DNA methyltransferase reaction, facilitate the compaction of both types of nucleosomes. The difference between the unmethylated and the methylated nucleosome persists within a broad range of salt concentrations, but vanishes under high magnesium concentrations. Reduced DNA backbone rigidity due to the presence of methyl groups is believed to contribute to the observed structural and dynamic differences. The observation of this study suggests that DNA methylation alone does not compact chromatin at the nucleosomal level and provides molecular details to understand the regulatory role of DNA methylation in gene expression.