Role of Histone Tails in Structural Stability of the Nucleosome

Biswas, Mithun; Voltz, Karine; Smith, Jeremy C.; Langowski, Jörg

doi:10.1371/journal.pcbi.1002279

Cited by 109 publications

(116 citation statements)

References 48 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…To study DNA unwrapping, we used the 1KX5 nucleosome with the histone tails removed (85), because the tails may hinder the unwrapping process. The condition of high pH was mimicked by setting all of the titratable sites to their deprotonated states.…”

Section: Methodological Detailsmentioning

confidence: 99%

“…Experimentally, it has been shown that under physiological conditions, the unstructured positively charged histone tails collapse onto the negatively charged DNA (83). It has also been shown that histone tails regulate nucleosome mobility and stability (84), and MD simulations have been used to study this regulatory mechanism (85).…”

Section: Nucleosome Histone Tail Collapsementioning

confidence: 99%

See 1 more Smart Citation

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Anandakrishnan

Drozdetski

Walker

et al. 2015

Biophysical Journal

172

192

View full text Add to dashboard Cite

Adequate sampling of conformation space remains challenging in atomistic simulations, especially if the solvent is treated explicitly. Implicit-solvent simulations can speed up conformational sampling significantly. We compare the speed of conformational sampling between two commonly used methods of each class: the explicit-solvent particle mesh Ewald (PME) with TIP3P water model and a popular generalized Born (GB) implicit-solvent model, as implemented in the AMBER package. We systematically investigate small (dihedral angle flips in a protein), large (nucleosome tail collapse and DNA unwrapping), and mixed (folding of a miniprotein) conformational changes, with nominal simulation times ranging from nanoseconds to microseconds depending on system size. The speedups in conformational sampling for GB relative to PME simulations, are highly system- and problem-dependent. Where the simulation temperatures for PME and GB are the same, the corresponding speedups are approximately onefold (small conformational changes), between ∼1- and ∼100-fold (large changes), and approximately sevenfold (mixed case). The effects of temperature on speedup and free-energy landscapes, which may differ substantially between the solvent models, are discussed in detail for the case of miniprotein folding. In addition to speeding up conformational sampling, due to algorithmic differences, the implicit solvent model can be computationally faster for small systems or slower for large systems, depending on the number of solute and solvent atoms. For the conformational changes considered here, the combined speedups are approximately twofold, ∼1- to 60-fold, and ∼50-fold, respectively, in the low solvent viscosity regime afforded by the implicit solvent. For all the systems studied, 1) conformational sampling speedup increases as Langevin collision frequency (effective viscosity) decreases; and 2) conformational sampling speedup is mainly due to reduction in solvent viscosity rather than possible differences in free-energy landscapes between the solvent models.

show abstract

Section: Methodological Detailsmentioning

confidence: 99%

Section: Nucleosome Histone Tail Collapsementioning

confidence: 99%

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Anandakrishnan

Drozdetski

Walker

et al. 2015

Biophysical Journal

172

192

View full text Add to dashboard Cite

show abstract

“…From the crystal structure, it can be seen that the C-terminal part of H2A (amino acids 80–119), including the α3- and αC-helices, forms a ladle shaped docking domain that constitutes an important interface for interaction with the (H3–H4) 2 -tetramer (8). The very C-terminal amino acids protrude from the globular nucleosome structure and interact with DNA, which is illustrated by molecular dynamics (MD) simulations, revealing stable hydrogen bonds between DNA and the lysines 118 and 119 in H2A (155). This is consistent with the recent finding that H2A monoubiquitination of these residues (Figure 2A) destabilizes nucleosomes during repair of UV-induced DNA damage (156), possibly by neutralization of the negative charge of the ε-amino group.…”

Section: The Influence Of H2a Variants On Nucleosome Stabilitymentioning

confidence: 99%

Histone H2A variants in nucleosomes and chromatin: more or less stable?

Bönisch

Hake

2012

Nucleic Acids Research

268

245

View full text Add to dashboard Cite

In eukaryotes, DNA is organized together with histones and non-histone proteins into a highly complex nucleoprotein structure called chromatin, with the nucleosome as its monomeric subunit. Various interconnected mechanisms regulate DNA accessibility, including replacement of canonical histones with specialized histone variants. Histone variant incorporation can lead to profound chromatin structure alterations thereby influencing a multitude of biological processes ranging from transcriptional regulation to genome stability. Among core histones, the H2A family exhibits highest sequence divergence, resulting in the largest number of variants known. Strikingly, H2A variants differ mostly in their C-terminus, including the docking domain, strategically placed at the DNA entry/exit site and implicated in interactions with the (H3–H4)2-tetramer within the nucleosome and in the L1 loop, the interaction interface of H2A–H2B dimers. Moreover, the acidic patch, important for internucleosomal contacts and higher-order chromatin structure, is altered between different H2A variants. Consequently, H2A variant incorporation has the potential to strongly regulate DNA organization on several levels resulting in meaningful biological output. Here, we review experimental evidence pinpointing towards outstanding roles of these highly variable regions of H2A family members, docking domain, L1 loop and acidic patch, and close by discussing their influence on nucleosome and higher-order chromatin structure and stability.

show abstract

“…Chromatin is a complex of DNA and histone tetramar proteins that form chromosomes within the nucleus of eukaryotic cells 42 . DNA does not appear in free strands for chromatin rather it is highly condensed and wrapped around histone tetramer proteins in order to fit compactly inside the nucleus 43 . Therefore, DNA strands in chromatin are less accessible for intercalation of Sgr as compared to free DNA strands in ctDNA which is clearly observable from our T-T absorption results.…”

Section: Efficiency Of Drug Release (%)=((A T-t Drug-aunp -A T-tmentioning

confidence: 99%

Development of a Triplet–Triplet Absorption Ruler: DNA- and Chromatin-Mediated Drug Molecule Release from a Nanosurface

Chakraborty¹,

Sau²,

Кузнецов

et al. 2016

J. Phys. Chem. B

View full text Add to dashboard Cite

Triplet-triplet (T-T) absorption spectroscopy has been used successfully as a molecular ruler to understand the actual release process of sanguinarine as a drug molecule from a gold nanoparticle surface in the presence of cell components, that is, DNA and chromatin. The obtained results have been verified by fluorescence and surface-enhanced Raman spectroscopy (SERS), and a plausible explanation has been put forward to describe the underestimation and overestimation of the percentage (%) of the release of drug molecules measured by fluorescence- and SERS-based techniques, respectively, over the highlighted T-T absorption spectroscopy. Because of the intrinsic nature of absorption, the reported T-T absorption spectroscopic assay overpowers fluorescence- and SERS-based assays, which are limited by the long-range interaction and nonlinear dependence of the concentration of analytes, respectively.

show abstract

Role of Histone Tails in Structural Stability of the Nucleosome

Cited by 109 publications

References 48 publications

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

Histone H2A variants in nucleosomes and chromatin: more or less stable?

Development of a Triplet–Triplet Absorption Ruler: DNA- and Chromatin-Mediated Drug Molecule Release from a Nanosurface

Contact Info

Product

Resources

About