DNA methylation, nucleosome formation and positioning

Abstract

Recent mapping of nucleosome positioning on several long gene regions subject to DNA methylation has identified instances of nucleosome repositioning by this base modification. The evidence for an effect of CpG methylation on nucleosome formation and positioning in chromatin is reviewed here in the context of the complex sequence-structure requirements of DNA wrapping around the histone octamer and the role of this epigenetic mark in gene repression.

Dynamics of Nucleosome Assembly and Effects of DNA Methylation

“…Some of the studies demonstrated altered translational positioning of nucleosomes (47)(48)(49) and inhibited nucleosome assembly (50, 51) upon methylation. A recent study reported that DNA affinity for histone octamer is increased upon DNA methylation (47,52). Another study showed that DNA methylation enhances nucleosome occupancy by increasing DNA affinity for histone octamer (32).…”

Nucleosome positioning in Arabidopsis

“…There have been few studies of the effect of DNA methylation on nucleosome positioning (Pennings et al, 2005). Nucleosomes containing H1 have been shown to form on methylated DNA in mouse (Ball et al, 1983).…”

Quantum Chemical Study for Radical-Induced DNA Effects and Damage

“…It was found that the C8 site of the purine ring was the main reaction site in dA and dG, and the C5 site of the pyrimidine ring was preferentially methylated in dC. [2][3][4][5] The relative yields of the methylated forms for the C 8 sites of dA and dG were about 10 times those of the methylated forms for the C 5 site of dC. A quantum chemical explanation is given for the differences in reactivity and the nature of the generated reactions, and a comparative analysis of the differences in reactivity with the radicals of each base pair in DNA was performed using a Gaussian program.…”

“…There is some similarity in the orbital shapes of complexes G-C and A-T, but the stabilization that results from orbital interaction differs. Therefore, reactions of complexes G-C and A-T that are present in DNA and radicals occur in the G fraction of complex G-C. Hix et al 5) demonstrated experimentally that complex A-T did not react and C 8 -Me-A was not obtained, mainly due to greater stability of the HOMO of complex A-T than that of complex G-C. 7,8) From the MO perspectives given in i) and ii), the following concepts (A-C) were identified.…”

“…A new concept of molecular interaction can be directly applicable to the manner of a CpG island part in DNA affected by radicals. 8,9) On the other hand, the quantum chemical preliminary calculations have shown that the methylation of complex G-C extend the distances between the N and O heteroatoms composed of hydrogen-bonded pairs of complex G-C. The results indicate that the cause of the DNA double helix break is the decreased hydrogen bonding between G and C molecules due to the methylation of complex G-C in DNA.…”