Abstract
BackgroundH2A.B, the most divergent histone variant of H2A, can significantly modulate nucleosome and chromatin structures. However, the related structural details and the underlying mechanism remain elusive to date. In this work, we built atomic models of the H2A.B-containing nucleosome core particle (NCP), chromatosome, and chromatin fiber. Multiscale modeling including all-atom molecular dynamics and coarse-grained simulations were then carried out for these systems.ResultsIt is found that sequence differences at the C-terminal tail, the docking domain, and the L2 loop, between H2A.B and H2A are directly responsible for the DNA unwrapping in the H2A.B NCP, whereas the N-terminus of H2A.B may somewhat compensate for the aforementioned unwrapping effect. The assembly of the H2A.B NCP is more difficult than that of the H2A NCP. H2A.B may also modulate the interactions of H1 with both the NCP and the linker DNA and could further affect the higher-order structure of the chromatin fiber.ConclusionsThe results agree with the experimental results and may shed new light on the biological function of H2A.B. Multiscale modeling may be a valuable tool for investigating structure and dynamics of the nucleosome and the chromatin induced by various histone variants.
Highlights
H2A.B, the most divergent histone variant of H2A, can significantly modulate nucleosome and chromatin structures
These two techniques are complementary to DNA is more relaxed in the H2A.B nucleosome core particle (NCP) Using the H2A NCP structure as the template, we built a structural model of H2A.B NCP (Fig. 1b) using homology modeling [23]
Experimental data have shown that the H2A.B NCP has different properties from the H2A NCP, and, among them, the most important feature is the highly dynamic DNA in the H2A.B NCP [9,10,11,12]
Summary
H2A.B, the most divergent histone variant of H2A, can significantly modulate nucleosome and chromatin structures. We built atomic models of the H2A.B-containing nucleosome core particle (NCP), chromatosome, and chromatin fiber. It is known that a nucleosome core particle (NCP) is composed of an octamer of canonical histones, including two copies each of H2A, H2B, H3, and H4 and approximately 146 base pairs of DNA wrapped around the octamer [2]. The NCPs. There are a number of ways to regulate the dynamic mode of nucleosome and chromatin, and one of them is to replace the canonical histones with histone variants. A histone variant has a more or less different amino acid sequence than the corresponding canonical histone, which may change the structure and dynamics of the nucleosome and the chromatin fiber [6]. Among all the canonical histones, H2A has the largest number of
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