Role of Histone Tails in Structural Stability of the Nucleosome (original) (raw)
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The role of histone tails in nucleosome stability: An electrostatic perspective
Computational and Structural Biotechnology Journal, 2020
We propose a methodology for the study of protein-DNA electrostatic interactions and apply it to clarify the effect of histone tails in nucleosomes. This method can be used to correlate electrostatic interactions to structural and functional features of protein-DNA systems, and can be combined with coarse-grained representations. In particular, we focus on the electrostatic field and resulting forces acting on the DNA. We investigate the electrostatic origins of effects such as different stages in DNA unwrapping, nucleosome destabilization upon histone tail truncation, and the role of specific arginines and lysines undergoing Post-Translational Modifications. We find that the positioning of the histone tails can oppose the attractive pull of the histone core, locally deform the DNA, and tune DNA unwrapping. Small conformational variations in the often overlooked H2A C-terminal tails had significant electrostatic repercussions near the DNA entry and exit sites. The H2A N-terminal tail exerts attractive electrostatic forces towards the histone core in positions where Polymerase II halts its progress. We validate our results with comparisons to previous experimental and computational observations.
Effect of histone H4 tail on nucleosome stability and internucleosomal interactions
Scientific Reports
Chromatin structure is dictated by nucleosome assembly and internucleosomal interactions. The tight wrapping of nucleosomes inhibits gene expression, but modifications to histone tails modulate chromatin structure, allowing for proper genetic function. The histone H4 tail is thought to play a large role in regulating chromatin structure. Here we investigated the structure of nucleosomes assembled with a tail-truncated H4 histone using Atomic Force Microscopy. We assembled tail-truncated H4 nucleosomes on DNA templates allowing for the assembly of mononucleosomes or dinucleosomes. Mononucleosomes assembled on nonspecific DNA led to decreased DNA wrapping efficiency. This effect is less pronounced for nucleosomes assembled on positioning motifs. Dinucleosome studies resulted in the discovery of two effects- truncation of the H4 tail does not diminish the preferential positioning observed in full-length nucleosomes, and internucleosomal interaction eliminates the DNA unwrapping effect....
Proteins: Structure, Function, and Bioinformatics, 2004
The present study provides insights on the dominant mechanisms of motions of the nucleosome core particle and the changes in its functional dynamics in response to histone variants. Comparative analysis of the global dynamics of nucleosomes with native and variant H2A histones, using normal mode analysis revealed that the dynamics of the nucleosome is highly symmetric, and its interaction with the nucleosomal DNA plays a vital role in its regulation. The collective dynamics of nucleosomes are predicted to be dominated by two types of large-scale motions: (1) a global stretching-compression of nucleosome along the dyad axis by which the nucleosome undergoes a breathing motion with a massive distortion of nucleosomal DNA, modulated by histone-DNA interactions; and (2) the flipping (or bending) of both the sides of the nucleosome in an out-of-plane fashion with respect to the dyad axis, originated by the highly dynamic N-termini of H3 and (H2A.Z-H2B) dimer in agreement with the experimentally observed perturbed dynamics of the particular N-terminus under physiological conditions. In general, the nucleosomes with variant histones exhibit higher mobilities and weaker correlations between internal motions compared to the nucleosome containing ordinary histones. The differences are more pronounced at the L1 and L2 loops of the respective monomers H2B and H2A, and at the N-termini of the monomers H3 and H4, all of which closely interact with the wrapping DNA.
Journal of molecular modeling, 2017
The roles of histone tails as substrates for reversible chemical modifications and dynamic cognate surfaces for the binding of regulatory proteins are well established. Despite these crucial roles, experimentally derived knowledge of the structure and possible binding sites of histone tails in chromatin is limited. In this study, we utilized molecular dynamics of isolated histone H3 N-terminal peptides to investigate its structure as a function of post-translational modifications that are known to be associated with defined chromatin states. We observed a structural preference for α-helices in isoforms associated with an inactive chromatin state, while isoforms associated with active chromatin states lacked α-helical content. The physicochemical effect of the post-translational modifications was highlighted by the interaction of arginine side-chains with the phosphorylated serine residues in the inactive isoform. We also showed that the isoforms exhibit different tail lengths, and, ...
bioRxiv, 2021
Apurinic/apyrimidinic sites are the most common DNA damage under physiological conditions. Yet, their structural and dynamical behavior within nucleosome core particles has just begun to be investigated, and show dramatic differences with the one of abasic sites in B-DNA. Clusters of two or more abasic sites are repaired even less efficiently and hence constitute hotspots of high mutagenicity notably due to enhanced double-strand breaks formation. Based on a X-ray structure of a 146-bp DNA wrapped onto a histone core, we investigate the structural behavior of two bistranded abasic sites positioned at mutational hotspots along microsecond-range molecular dynamics simulations. Our simulations allow us to probe histone tails interactions at clustered abasic sites locations, with a definitive assignment of the key residues in-volved in the NCP-catalyzed formation of DNA–protein cross-linking in line with recent experimental findings, and pave the way towards a systematic assessment of h...
Journal of the American Chemical Society, 2009
The N-terminal tail domains (NTDs) of histones play important roles in the formation of higherorder structures of chromatin and the regulation of gene functions. Although the structure of the nucleosome core particle has been determined by X-ray crystallography at near-atomic resolution, the histone tails are not observed in this structure. Here, we demonstrate that large quantities of nucleosome arrays with well-defined DNA positioning can be reconstituted using specific DNA sequences and recombinant isotope-labeled histones, allowing for the investigation of NTD conformations by amide hydrogen exchange and multi-dimensional nuclear magnetic resonance (NMR) methods. We examined the NTD of Drosophila melanogaster histones H3 in condensed
Apurinic/apyrimidinic sites are the most common DNA damage under physiological conditions. Yet, their structural and dynamical behavior within nucleosome core particles has just begun to be investigated, and show dramatic differences with the one of abasic sites in B-DNA. Clusters of two or more abasic sites are repaired even less efficiently and hence constitute hotspots of high mutagenicity notably due to enhanced double-strand breaks formation. Based on a Xray structure of a 146-bp DNA wrapped onto a histone core, we investigate the structural behavior of two bistranded abasic sites positioned at mutational hotspots along microsecondrange molecular dynamics simulations. Our simulations allow us to probe histone tails interactions at clustered abasic sites locations, with a definitive assignment of the key residues involved in the NCP-catalyzed formation of DNA-protein crosslinking in line with recent experimental findings, and pave the way towards a systematic assessment of histone tails response to DNA lesions.
Journal of Biological Chemistry, 2010
In eukaryotic nuclei the majority of genomic DNA is believed to exist in higher order chromatin structures. Nonetheless, the nature of direct, long range nucleosome interactions that contribute to these structures is poorly understood. To determine whether these interactions are directly mediated by contacts between the histone H4 amino-terminal tail and the acidic patch of the H2A/H2B interface, as previously demonstrated for short range nucleosomal interactions, we have characterized the extent and effect of disulfide cross-linking between residues in histones contained in different strands of nucleosomal arrays. We show that in 208-12 5 S rDNA and 601-177-12 nucleosomal array systems, direct interactions between histones H4-V21C and H2A-E64C can be captured. This interaction depends on the extent of initial cross-strand association but does not require these specific residues, because interactions with residues flanking H4-V21C can also be captured. Additionally, we find that trapping H2A-H4 intra-array interactions antagonizes the ability of these arrays to undergo intermolecular self-association.