Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.
Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.
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DOI：
10.1371/journal.pcbi.1003354
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发表时间：
2013
影响因子：
4.3
通讯作者：
Orozco M
中科院分区：
文献类型：
--
作者：
Portella G;Battistini F;Orozco M
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. In Eukaryotic cells, control of the patterns of DNA cytosine methylation – a mechanism that acts on top of the genetic code – plays a key role in the regulation of gene expression. The large prevalence of DNA methylation in vivo, suggests a connection between the physical properties of methylated and un-methylated DNA with the control of gene expression. In this work we investigate the physical implications of DNA methylation in nucleosomal DNA, in particular its preferred location with respect to the nucleosome core-particle and the consequences of DNA methylation for the accessibility of the genetic material. We find that methylated DNA is less prone to form nucleosomes due to a reduced elasticity, especially when all methyl groups are pointing outwards from the nucleosome core, and that multiple methylation could give rise to changes in nucleosome positioning.
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影响因子：
14.9
作者：
Lavery R;Moakher M;Maddocks JH;Petkeviciute D;Zakrzewska K
通讯作者：
Zakrzewska K
影响因子：
15
作者：
Lee, Ju Yeon;Lee, Tae-Hee
通讯作者：
Lee, Tae-Hee
影响因子：
14.9
作者：
EHRLICH, M;GAMASOSA, MA;GEHRKE, C
通讯作者：
GEHRKE, C
影响因子：
4.4
作者：
Deniz O;Flores O;Battistini F;Pérez A;Soler-López M;Orozco M
通讯作者：
Orozco M
影响因子：
64.8
作者：
Meissner, Alexander;Mikkelsen, Tarjei S.;Gu, Hongcang;Wernig, Marius;Hanna, Jacob;Sivachenko, Andrey;Zhang, Xiaolan;Bernstein, Bradley E.;Nusbaum, Chad;Jaffe, David B.;Gnirke, Andreas;Jaenisch, Rudolf;Lander, Eric S.
通讯作者：
Lander, Eric S.