Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.

Cytosine methylation is one of the most important epigenetic marks that regulate the process of gene expression. Here, we have examined the effect of epigenetic DNA methylation on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found that methylation of...

Description complète

Enregistré dans:
Détails bibliographiques
Auteurs principaux: Guillem Portella, Federica Battistini, Modesto Orozco
Format: article
Langue:EN
Publié: Public Library of Science (PLoS) 2013
Sujets:
Accès en ligne:https://doaj.org/article/029f6b54fbd841eaafacdc02fb87eabd
Tags: Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
Description
Résumé:Cytosine methylation is one of the most important epigenetic marks that regulate the process of gene expression. Here, we have examined the effect of epigenetic DNA methylation on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found that methylation of CpG steps destabilizes nucleosomes, especially when these are placed in sites where the DNA minor groove faces the histone core. The larger stiffness of methylated CpG steps is a crucial factor behind the decrease in nucleosome stability. Methylation changes the positioning and phasing of the nucleosomal DNA, altering the accessibility of DNA to regulatory proteins, and accordingly gene functionality. Our theoretical calculations highlight a simple physical-based explanation on the foundations of epigenetic signaling.