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 d...

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Bibliographic Details
Published in:Structure (London) 2023-02, Vol.31 (2), p.201-212.e5
Main Authors: Louro, Jaime Alegrio, Boopathi, Ramachandran, Beinsteiner, Brice, Mohideen Patel, Abdul Kareem, Cheng, Tat Cheung, Angelov, Dimitar, Hamiche, Ali, Bendar, Jan, Kale, Seyit, Klaholz, Bruno P., Dimitrov, Stefan
Format: Article
Language:English
Subjects:
Chemical Sciences
Chromatin
cryo-EM
DNA - metabolism
Histones - metabolism
Life Sciences
linker histone H1
molecular dynamics
nucleosome
Nucleosomes
Protein Binding
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Summary: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. [Display omitted] •Linker histone H1 CTD collapses on one linker or another depending on-dyad DNA sequence•H1 restricts linker DNA flexibility but reveals partial asymmetrical unwrapping•MD simulations show that the CTD collapse and H1 GD orientation could be coupled Alegrio Louro et al. report the cryo-EM structure of a nucleosome reconstituted on a palindromic version of 197 bp Widom 601 DNA complexed with linker histone H1. H1 CTD collapses to the proximal linker and MD simulations show that this is linked to the orientation of the H1 globular domain.
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2022.12.005