Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

Abstract Nucleosomes are structural units of the chromosome consisting of DNA wrapped around histone proteins, and play important roles in compaction and regulation of the chromatin structure. While the structure and dynamics of canonical nucleosomes have been studied extensively, those of nucleosomes in intermediate states, that occur when their structure or positioning is modulated, have been less understood. In particular, the dynamic features of partially disassembled nucleosomes have not been discussed in previous studies. Using all-atom molecular dynamics simulations, in this study, we investigated the dynamics and stability of nucleosome structures lacking a histone-dimer. DNA in nucleosomes lacking a histone H2A/H2B dimer was drastically deformed due to loss of local interactions between DNA and histones. In contrast, conformation of DNA in nucleosomes lacking H3/H4 was similar to the canonical nucleosome, as the H2A C-terminal domain infiltrated the space originally occupied by the dissociated H3/H4 histones and stabilized DNA in close proximity. Our results suggest that, besides histone chaperones, the intrinsic dynamics of nucleosomes support the exchange of H2A/H2B, which is significantly more frequent than that of H3/H4. Statement of Significance Eukaryotic chromosomes are composed of nucleosomes, in which the DNA wraps around the core histone proteins. To enable transcription and replication of DNA, or to modulate these functions by exchange of histones, nucleosomes should be at least partially disassembled, as evidenced by the observation of nucleosome structures lacking an H2A/H2B histone dimer by crystallography. The dynamic behavior of nucleosomes in such intermediate states may affect gene expression and repair, however it has not been completely elucidated so far. In this study, we adopted molecular dynamics simulations to analyze the conformational changes in partially disassembled nucleosomes. Enhanced structural fluctuations of DNA were observed in these nucleosomes, which may, as well as specific histone chaperones, support the exchange of H2A/H2B.