Chromatosome Structure and Dynamics from Molecular Simulations

Abstract

Chromatosomes are fundamental units of chromatin structure that are formed when a linker histone protein binds to a nucleosome. The positioning of the linker histone on the nucleosome influences the packing of chromatin. Recent simulations and experiments have shown that chromatosomes adopt an ensemble of structures that differ in the geometry of the linker histone–nucleosome interaction. In this article we review the application of Brownian, Monte Carlo, and molecular dynamics simulations to predict the structure of linker histone–nucleosome complexes, to study the binding mechanisms involved, and to predict how this binding affects chromatin fiber structure. These simulations have revealed the sensitivityof the chromatosome structure to variations in DNA and linker histone sequence, as well as to posttranslational modifications, thereby explaining the structural variability observed in experiments. We propose that a concerted application of experimental and computational approaches will reveal the determinants of chromatosome structural variability and how it impacts chromatin packing.

Linker histone defines structure and self-association behaviour of the 177 bp human chromatosome

“…Numerous structural studies on isolated nucleosomes using linker histone variants from fruit fly, frog, chicken, mouse, and human have produced various structural models for linker histones binding (for reviews see e.g. [17][18][19][20][21][22] ). The globular domain of the linker chicken histone H5 bound to a 167 bp nucleosome displayed a symmetric on dyad linker histone binding mode in the 3.5 Å X-ray structure 23 .…”

Extended and dynamic linker histone-DNA interactions control chromatosome compaction

“…The fact that H1 survives the unzipping when bound to a single-linker nucleosome, provides and additional evidence for the resilience to DNA unzipping of an H1 contact at the dyad. Collectively, our study suggests that a single H1 subtype can adopt both the on-dyad and off-dyad orientations, with the on-dyad being more energetically favorable 11,58 . As the off-dyad mode is associated with a less compact nucleosome, transition to this state can be fine-tuned by cellular cues to directly regulate H1 contacts at the dyad or with the linker DNA.…”

“…Further organization is supported by one of several linker histones (H1s) 6 , which bind the nucleosome to form a chromatosome 7 , facilitating the formation of higher-order structures 8,9 and promoting liquid-liquid phase separation 10 . Despite the central role that linker histones play in organizing and regulating the chromatin structure, a molecular understanding of their function is only starting to emerge [11][12][13][14] . Eleven subtypes of linker histones have been identified in humans and mice, and they share a conserved structure, composed of a winged-helix globular domain (GD) flanked by unstructured and intrinsically disordered short N-terminal (NTD) and long C-terminal (CTD) domains 12,15 .…”

CENP-A nucleosome—a chromatin-embedded pedestal for the centromere: lessons learned from structural biology

“…It is clear, ever since Lowary and Widom identified super-positioning 601 sequence for canonical nucleosome [ 58 ] that the DNA sequence affects the nucleosome stability. However, although computational methods are starting to address DNA sequence–nucleosome structure relationship [ 66 ] it is still extremely difficult to study experimentally at high resolution. Until recently, the majority of high-resolution nucleosome structures were obtained by X-ray crystallography, which imposes the constraints of crystal packing which, in turn, interferes with the high-quality crystal formation of nucleosomes wrapped with array of different sequences.…”