Cytosine methylation alters DNA mechanical properties

Severin, Philip M. D.; Zou, Xueqing; Gaub, Hermann E.; Schulten, Klaus

doi:10.1093/nar/gkr578

Cited by 126 publications

(142 citation statements)

References 72 publications

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“…Nevertheless, irregular conformations were seen quite commonly in vivo in studies by electron and optical microscopy (for example [31,32]) ( Figure 3B) and were also predicted by simulation of the response to crowding of linear polyelectrolyte polymers [9,33] (Figure 3A) and by considering that chromosomes resemble block copolymers [34,35] with interspersed regions of repeated DNA sequences [36], methylated cytosine-containing DNA which has particular conformational properties [37,38], and nucleosomes containing variant or modified histones which influence fiber interactions [39,40]. These discrepancies have been resolved by recent cryo-electron microscopy and X-ray scattering studies, which show conclusively that chromatin fibers exist in vivo in a disordered, interdigitated state resembling a polymer melt [41].…”

Section: Structure and Packing Of Chromosomes Chromatin Fibersmentioning

confidence: 59%

Structures and functions in the crowded nucleus: new biophysical insights

Hancock

2014

Front. Phys.

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Concepts and methods from the physical sciences have catalyzed remarkable progress in understanding the cell nucleus in recent years. To share this excitement with physicists and encourage their interest in this field, this review offers an overview of how the physics which underlies structures and functions in the nucleus is becoming more clear thanks to methods which have been developed to simulate and study macromolecules, polymers, and colloids. The environment in the nucleus is very crowded with macromolecules, making entropic (depletion) forces major determinants of interactions. Simulation and experiments are consistent with their key role in forming membraneless compartments such as nucleoli, PML and Cajal bodies, and discrete "territories" for chromosomes. The chromosomes, giant linear polyelectrolyte polymers, exist in vivo in a state like a polymer melt. Looped conformations are predicted in crowded conditions, and have been confirmed experimentally and are central to the regulation of gene expression. Polymer theory has revealed how the chromosomes are so highly compacted in the nucleus, forming a "crumpled globule" with fractal properties which avoids knots and entanglements in DNA while allowing facile accessibility for its replication and transcription. Entropic repulsion between looped polymers can explain the confinement of each chromosome to a discrete region of the nucleus. Crowding and looping are predicted to facilitate finding the specific targets of factors which modulate activities of DNA. Simulation shows that entropic effects contribute to finding and repairing potentially lethal double-strand breaks in DNA by increasing the mobility of the broken ends, favoring their juxtaposition for repair. Signaling pathways are strongly influenced by crowding, which favors a processive mode of response (consecutive reactions without releasing substrates). This new information contributes to understanding the sometimes counter-intuitive consequences and the evolutionary advantages of a crowded environment in the nucleus.

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Section: Structure and Packing Of Chromosomes Chromatin Fibersmentioning

confidence: 59%

Structures and functions in the crowded nucleus: new biophysical insights

Hancock

2014

Front. Phys.

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“…It is not known whether there are any DNA-binding proteins in E. coli with transcriptional regulatory roles whose activities are dependent on the methylation state of the substrate DNA. However, cytosine methylation also alters the mechanical properties of DNA 52 , and this might have profound consequences on transcription.…”

Section: Discussionmentioning

confidence: 99%

Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription

et al. 2012

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DnA cytosine methylation regulates gene expression in mammals. In bacteria, its role in gene expression and genome architecture is less understood. Here we perform high-throughput sequencing of bisulfite-treated genomic DnA from Escherichia coli K12 to describe, for the first time, the extent of cytosine methylation of bacterial DnA at single-base resolution. Whereas most target sites (C m CWGG) are fully methylated in stationary phase cells, many sites with an extended CC m CWGG motif are only partially methylated in exponentially growing cells. We speculate that these partially methylated sites may be selected, as these are slightly correlated with the risk of spontaneous, non-synonymous conversion of methylated cytosines to thymines. microarray analysis in a cytosine methylation-deficient mutant of E. coli shows increased expression of the stress response sigma factor Rpos and many of its targets in stationary phase. Thus, DnA cytosine methylation is a regulator of stationary phase gene expression in E. coli.

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“…Bianchi & Zangi explored the impact of cytosine methylation on base flipping [63], and the mechanisms of recognition by proteins of DNA containing MeC [97]. Broyde and coworkers used QM/MM to explore basic structural properties of DNA containing MeC [98], and Carvalho and coworkers [99] confirmed previous claims by other authors [100,101] that methylation largely alters the elastic properties of DNA. These studies suggested that methylation-related changes might affect the nucleosome binding, a hypothesis that has been confirmed in recent studies [102,103].…”

Section: Atomistic Studiesmentioning

confidence: 65%

Multiscale simulation of DNA

Dans¹,

Walther

Gómez

et al. 2016

Current Opinion in Structural Biology

145

131

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DNA is not only among the most important molecules in life, but a meeting point for biology, physics and chemistry, being studied by numerous techniques. Theoretical methods can help in gaining a detailed understanding of DNA structure and function, but their practical use is hampered by the multiscale nature of this molecule. In this regard, the study of DNA covers a broad range of different topics, from sub-Angstrom details of the electronic distributions of nucleobases, to the mechanical properties of millimeter-long chromatin fibers. Some of the biological processes involving DNA occur in femtoseconds, while others require years. In this review, we describe the most recent theoretical methods that have been considered to study DNA, from the electron to the chromosome, enriching our knowledge on this fascinating molecule.

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Cytosine methylation alters DNA mechanical properties

Cited by 126 publications

References 72 publications

Structures and functions in the crowded nucleus: new biophysical insights

Structures and functions in the crowded nucleus: new biophysical insights

Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription

Multiscale simulation of DNA

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