Hydrophobicity of methylated DNA as a possible mechanism for gene silencing

Kaur, Parminder; Plochberger, Birgit; Costa, Peter I. De; Cope, Stephanie M.; Vaiana, Sara M.; Lindsay, Stuart

doi:10.1088/1478-3975/9/6/065001

Cited by 31 publications

(50 citation statements)

References 29 publications

(69 reference statements)

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“…Although the findings of this paper can be a major stepping stone towards understanding the effects of DNA methylation on chromosome compactness, other factors, such as interactions between nucleosomes, effective lengths of linker DNA and interactions with linker histone proteins, have to be accounted for to correlate the observed changes in mono-nucleosome conformation with chromosome compactness. This additional information will be essential to reconcile the controversial evidences as to the effects of DNA methylation on chromosome compactness in literature383940.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Regulated Nucleosome Dynamics

Jimenez-Useche

Tian

et al. 2013

Sci Rep

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A strong correlation between nucleosome positioning and DNA methylation patterns has been reported in literature. However, the mechanistic model accounting for the correlation remains elusive. In this study, we evaluated the effects of specific DNA methylation patterns on modulating nucleosome conformation and stability using FRET and SAXS. CpG dinucleotide repeats at 10 bp intervals were found to play different roles in nucleosome stability dependent on their methylation states and their relative nucleosomal locations. An additional (CpG)5 stretch located in the nucleosomal central dyad does not alter the nucleosome conformation, but significant conformational differences were observed between the unmethylated and methylated nucleosomes. These findings suggest that the correlation between nucleosome positioning and DNA methylation patterns can arise from the variations in nucleosome stability dependent on their sequence and epigenetic content. This knowledge will help to reveal the detailed role of DNA methylation in regulating chromatin packaging and gene transcription.

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Section: Discussionmentioning

confidence: 99%

DNA Methylation Regulated Nucleosome Dynamics

Jimenez-Useche

Tian

et al. 2013

Sci Rep

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“…Along the same lines, Choy et al (2010) suggest that the enhanced rigidity of methylated DNA leads to more compact and closed nucleosomes. Methylated DNA was also shown to be more difficult to remove from a nucleosome (Kaur et al, 2012). By combining data from genome-wide nucleosome positioning with available DNA methylation maps, Chodavarapu et al (2010) have shown that there is a small increase (about 1.2%, from 75 to 76.2%) in preference of nucleosome positioning for methylated DNA.…”

Section: Relationship Between Nucleosome Positioning and Dna Methylationmentioning

confidence: 99%

The physics of epigenetics

et al. 2016

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In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multi-scale physical mechanisms that govern the biological processes behind the initiation, spreading and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional changes, typically in the the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature under this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping and transmitting this crucial "epigenetic landscape". This new perspective not only allows to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.

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“…Methylation of cytosine is an epigenetic modification essential for the regulation of many biological processes, and DNA methylation affects nucleosome shape and dynamics. Single molecule Förster resonance energy transfer (FRET), solid‐state nuclear magnetic resonance (NMR), and atomic force microscopy (AFM) studies have indicated that the nucleosome rigidifies upon DNA methylation. An increase in the stiffness of bare DNA upon methylation was seen in DNA circularization experiments,4b, gel studies, and Fourier transform infrared spectroscopy (FTIR) experiments, and methylation was shown to alter the curvature of DNA in electrophoresis .…”

Section: Introductionmentioning

confidence: 99%

Enhanced sampling simulations of DNA step parameters

Karolak

Vaart

2014

J Comput Chem

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A novel approach for the selection of step parameters as reaction coordinates in enhanced sampling simulations of DNA is presented. The method uses three atoms per base and does not require coordinate overlays or idealized base pairs. This allowed for a highly efficient implementation of the calculation of all step parameters and their Cartesian derivatives in molecular dynamics simulations. Good correlation between the calculated and actual twist, roll, tilt, shift, and slide parameters is obtained, while the correlation with rise is modest. The method is illustrated by its application to the methylated and unmethylated 5'-CATGTGACGTCACATG-3' double stranded DNA sequence. One-dimensional umbrella simulations indicate that the flexibility of the central CG step is only marginally affected by methylation.

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Hydrophobicity of methylated DNA as a possible mechanism for gene silencing

Cited by 31 publications

References 29 publications

DNA Methylation Regulated Nucleosome Dynamics

DNA Methylation Regulated Nucleosome Dynamics

The physics of epigenetics

Enhanced sampling simulations of DNA step parameters

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