Conformations of Linker Histone H1 Bound to Nucleosome Arrays

Linker histone H1 plays crucial roles in nucleosome compaction and chromatin condensation. The highly basic C-terminal domain (CTD) of H1 interacts strongly with DNA, a critical aspect of its contribution to H1 function. Despite its critical roles in gene packaging in chromatin where nucleosomes are linked as an array, how H1 CTD interacts with nucleosome arrays remain poorly understood. Here we report a single-molecule FRET study of the conformation and conformational dynamics of the CTD of H1 bound to a 12-mer nucleosome array. According to our results, H1 CTDs within a nucleosome array show signs of highly heterogeneous conformations that are overall more extended and dynamic than that bound to a mono-nucleosome. This observation suggests that H1 CTD interacts randomly with two or more DNA linkers across nucleosomes in an array. This suggestion is further supported by our observation that these domains become more condensed and less dynamic as the arrays become less condensed at a lower NaCl concentration. Our results also suggest that histone H3 and H4 acetylation mimetics and tailless H3 result in H1 CTD interacting less with multiple linkers as they induce a less condensed structure of nucleosome arrays, thereby driving H1 CTD back to its own nucleosome. Our data support that H1 CTD interacts non-specifically with DNA linkers that are either local or distal and that modifications of the H3 and H4 tail domains can regulate H1-mediated chromatin condensation at both the nucleosome and nucleosome array levels.