Nucleosome dyad determines the H1 C-terminus collapse on distinct DNA arms

Nucleosomes are symmetric structures. However, binding of linker histones generates an inherently asymmetric H1-nucleosome complex, and whether this asymmetry is transmitted to the overall nucleosome structure, and therefore also to chromatin, is unclear. Efforts to investigate potential asymmetry due to H1s have been hampered by the DNA sequence, which naturally differs in each gyre. To overcome this issue, we designed and analyzed by cryo-EM a nucleosome reconstituted with a palindromic (601L) 197-bp DNA. As in the non-palindromic 601 sequence, H1 restricts linker DNA flexibility but reveals partial asymmetrical unwrapping. However, in contrast to the non-palindromic nucleosome, in the palindromic nucleosome H1 CTD collapses to the proximal linker. Molecular dynamics simulations show that this could be dictated by a slightly tilted orientation of the globular domain (GD) of H1, which could be linked to the DNA sequence of the nucleosome dyad.

Automated summary

Binding of linker histones generates an asymmetric H1-nucleosome complex, and whether this asymmetry is transmitted to the overall nucleosome structure is unclear. We designed and analyzed a nucleosome with a palindromic DNA sequence to investigate potential asymmetry due to H1. The results showed that H1 restricts linker DNA flexibility and reveals partial asymmetrical unwrapping, but in the palindromic nucleosome, H1 CTD collapses to the proximal linker.