scholarly journals Histone dynamics mediate DNA unwrapping and sliding in nucleosomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Grigoriy A. Armeev ◽  
Anastasiia S. Kniazeva ◽  
Galina A. Komarova ◽  
Mikhail P. Kirpichnikov ◽  
Alexey K. Shaytan
Keyword(s):  
Building Blocks ◽  
Dna Dynamics ◽  
Conformational Variability ◽  
Nucleosome Core ◽  
Nucleosome Dynamics ◽  
Nucleosome Core Particles ◽  
Nucleosomal Dna ◽  
Dna Base ◽  
Dna Unwrapping ◽  
Dynamics Simulations

AbstractNucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ∼147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucleosomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.

scholarly journals Histone dynamics mediate DNA unwrapping and sliding in nucleosomes: insights from multi-microsecond molecular dynamics simulations

2021 ◽  
Author(s):  
Grigoriy A. Armeev ◽  
Anastasia S. Kniazeva ◽  
Galina A. Komarova ◽  
Mikhail P. Kirpichnikov ◽  
Alexey K. Shaytan
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Building Blocks ◽  
Dna Dynamics ◽  
Conformational Variability ◽  
Nucleosome Core ◽  
Nucleosome Dynamics ◽  
Nucleosomal Dna ◽  
Dna Unwrapping ◽  
Dynamics Simulations

AbstractNucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ~147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucle-osomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.We developed a web site for an interactive preview of molecular dynamics trajectories at https://intbio.github.io/Armeev_et_al_2021.

scholarly journals DNA methylation cues in nucleosome geometry, stability, and unwrapping

2021 ◽  
Author(s):  
Shuxiang Li ◽  
Yunhui Peng ◽  
David Landsman ◽  
Anna Panchenko
Keyword(s):  
Conformational Changes ◽  
Cytosine Methylation ◽  
Epigenetic Mark ◽  
Nucleosome Assembly ◽  
Functional Studies ◽  
Nucleosome Dynamics ◽  
Nucleosomal Dna ◽  
Dna Unwrapping ◽  
Dynamics Simulations ◽  
Eukaryotic Organisms

Cytosine methylation at the 5-carbon position is an essential DNA epigenetic mark in many eukaryotic organisms. Although countless structural and functional studies of cytosine methylation have been reported in both prokaryotes and eukaryotes, our understanding of how it influences the nucleosome assembly, structure, and dynamics remains obscure. Here we investigated the effects of cytosine methylation at CpG sites on nucleosome dynamics and stability. By applying long molecular dynamics simulations (five microsecond long trajectories, 60 microseconds in total), we generated extensive atomic level conformational full nucleosome ensembles. Our results revealed that methylation induces pronounced changes in geometry for both linker and nucleosomal DNA, leading to a more curved, under-twisted DNA, shifting the population equilibrium of sugar-phosphate backbone geometry. These conformational changes are associated with a considerable enhancement of interactions between methylated DNA and the histone octamer, doubling the number of contacts at some key arginines. H2A and H3 tails play important roles in these interactions, especially for DNA methylated nucleosomes. This, in turn, prevents a spontaneous DNA unwrapping of 3-4 helical turns for the methylated nucleosome with truncated histone tails, otherwise observed in the unmethylated system on several microsecond time scale.

scholarly journals Predicting near-UV electronic circular dichroism in nucleosomal DNA by means of DFT response theory

2015 ◽  
Vol 17 (34) ◽  
pp. 21866-21879 ◽  
Author(s):  
Patrick Norman ◽  
Joseph Parello ◽  
Prasad L. Polavarapu ◽  
Mathieu Linares
Keyword(s):  
Circular Dichroism ◽  
Density Functional ◽  
Time Dependent ◽  
Functional Theory ◽  
Electronic Circular Dichroism ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Nucleosomal Dna ◽  
Circular Dichroïsm ◽  
Dependent Density

It is demonstrated that time-dependent density functional theory (DFT) calculations can accurately predict changes in near-UV electronic circular dichroism (ECD) spectra of DNA as the structure is altered from the linear (free) B-DNA form to the supercoiled N-DNA form found in nucleosome core particles.

scholarly journals Nucleosomal embedding reshapes the dynamics of abasic sites

2020 ◽  
Author(s):  
Emmanuelle Bignon ◽  
Victor Claerbout ◽  
Tao Jiang ◽  
Christophe Morell ◽  
Natacha Gillet ◽  
...  
Keyword(s):  
Conformational Dynamics ◽  
Dna Lesions ◽  
Nucleosome Core ◽  
Abasic Sites ◽  
Nucleosomal Dna ◽  
Cross Links ◽  
Ap Sites ◽  
Base Excision ◽  
Dynamics Simulations ◽  
The Impact

ABSTRACTApurinic/apyrimidinic (AP) sites are the most common DNA lesions, which benefit from a most efficient repair by the base excision pathway. The impact of losing a nucleobase on the conformation and dynamics of B-DNA is well characterized. Yet AP sites seem to present an entirely different chemistry in nucleosomal DNA, with lifetimes reduced up to 100-fold, and the much increased formation of covalent DNA-protein cross-links, refractory to repair. We report microsecond range, all-atom molecular dynamics simulations that capture the conformational dynamics of AP sites and their tetrahydrofuran analogs at two symmetrical positions within a nucleosome core particle, starting from a recent crystal structure. Different behaviours between the deoxyribo-based and tetrahydrofuran-type abasic sites are evidenced. The two solvent-exposed lesion sites present contrasted extrahelicities, revealing the crucial role of the position of a defect around the histone core. Our all-atom simulations also identify and quantify the occurrence of several spontaneous, non-covalent interactions between AP and positively-charged residues from the histones H2A and H2B tails that prefigure DNA-protein cross-links. This study paves the way towards an in silico mapping of DNA-protein cross-links.

scholarly journals Lysine succinylation on non-histone chromosomal protein HMG-17 (HMGN2) regulates nucleosomal DNA accessibility by disrupting HMGN2-nucleosome association

2021 ◽  
Author(s):  
Yihang Jing ◽  
Gaofei Tian ◽  
Xiaoyu Qin ◽  
Zheng Liu ◽  
Xiang David Li
Keyword(s):  
Posttranslational Modification ◽  
Chromosomal Protein ◽  
Histone Proteins ◽  
Dna Accessibility ◽  
Nucleosome Dynamics ◽  
Lysine Succinylation ◽  
Nucleosomal Dna ◽  
Chromatin Proteins ◽  
Dna Unwrapping

Lysine succinylation (Ksucc) is a novel posttranslational modification that frequently occurs on chromatin proteins including histones and non-histone proteins. Histone Ksucc affects nucleosome dynamics by increasing DNA unwrapping rate and...

scholarly journals Local DNA Sequence Controls Asymmetry of DNA Unwrapping from Nucleosome Core Particles

2018 ◽  
Vol 115 (5) ◽  
pp. 773-781 ◽  
Author(s):  
Alexander W. Mauney ◽  
Joshua M. Tokuda ◽  
Lisa M. Gloss ◽  
Oscar Gonzalez ◽  
Lois Pollack
Keyword(s):  
Dna Sequence ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Dna Unwrapping ◽  
Core Particles

scholarly journals Trajectories of microsecond molecular dynamics simulations of nucleosomes and nucleosome core particles

Data in Brief ◽  
2016 ◽  
Vol 7 ◽  
pp. 1678-1681 ◽  
Author(s):  
Alexey K. Shaytan ◽  
Grigoriy A. Armeev ◽  
Alexander Goncearenco ◽  
Victor B. Zhurkin ◽  
David Landsman ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
Dynamics Simulations ◽  
Core Particles

scholarly journals The effect of linker DNA on the structure and interaction of nucleosome core particles

Soft Matter ◽  
2018 ◽  
Vol 14 (45) ◽  
pp. 9096-9106 ◽  
Author(s):  
Yen-Chih Huang ◽  
Chun-Jen Su ◽  
Nikolay Korolev ◽  
Nikolay V. Berezhnoy ◽  
Sai Wang ◽  
...  
Keyword(s):  
Small Angle ◽  
Core Particle ◽  
Nucleosome Core Particle ◽  
X Ray ◽  
Nucleosome Core ◽  
Nucleosome Core Particles ◽  
X Ray Scattering ◽  
Nucleosomal Dna ◽  
The Impact

Small angle X-ray scattering reveals linker DNA-induced partial unwrapping of nucleosomal DNA on the nucleosome core particle (NCP) and the impact on NCP interaction demonstrating the crucial role of linker DNA.

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