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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.23.609244
preprint
1
Article
HMGB1 restores a dynamic chromatin environment in the presence of linker histone by deforming nucleosomal DNA
Saunders Hayden S. http://orcid.org/0000-0002-7582-3031

Chio Un Seng
Moore Camille M.
Ramani Vijay
Cheng Yifan
Narlikar Geeta J
24 8 2024
2024.08.23.609244https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.23.609244
nihpp-2024.08.23.609244.pdf
Abstract

The essential architectural protein HMGB1 increases accessibility of nucleosomal DNA and counteracts the effects of linker histone H1. However, HMGB1 is less abundant than H1 and binds nucleosomes more weakly raising the question of how HMGB1 effectively competes with H1. Here, we show that HMGB1 rescues H1’s inhibition of nucleosomal DNA accessibility without displacing H1. HMGB1 also increases the dynamics of condensed, H1-bound chromatin. Cryo-EM shows that HMGB1 binds at internal locations on a nucleosome and locally distorts the DNA. These sites, which are away from the binding site of H1, explain how HMGB1 and H1 co-occupy a nucleosome. Our findings lead to a model where HMGB1 counteracts the activity of H1 by distorting nucleosomal DNA and by contacting the H1 C-terminal tail. Compared to direct competition, nucleosome co-occupancy by HMGB1 and H1 allows a greater diversity of dynamic chromatin states and may be generalizable to other chromatin regulators.
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