Single-stranded nucleic acid binding and coacervation by linker histone H1.
| Publication Type | Academic Article |
| Authors | Leicher R, Osunsade A, Chua G, Faulkner S, Latham A, Watters J, Nguyen T, Beckwitt E, Christodoulou-Rubalcava S, Young P, Zhang B, David Y, Liu S |
| Journal | Nat Struct Mol Biol |
| Volume | 29 |
| Issue | 5 |
| Pagination | 463-471 |
| Date Published | 04/28/2022 |
| ISSN | 1545-9985 |
| Keywords | Histones, Nucleosomes |
| Abstract | The H1 linker histone family is the most abundant group of eukaryotic chromatin-binding proteins. However, their contribution to chromosome structure and function remains incompletely understood. Here we use single-molecule fluorescence and force microscopy to directly visualize the behavior of H1 on various nucleic acid and nucleosome substrates. We observe that H1 coalesces around single-stranded DNA generated from tension-induced DNA duplex melting. Using a droplet fusion assay controlled by optical tweezers, we find that single-stranded nucleic acids mediate the formation of gel-like H1 droplets, whereas H1-double-stranded DNA and H1-nucleosome droplets are more liquid-like. Molecular dynamics simulations reveal that multivalent and transient engagement of H1 with unpaired DNA strands drives their enhanced phase separation. Using eGFP-tagged H1, we demonstrate that inducing single-stranded DNA accumulation in cells causes an increase in H1 puncta that are able to fuse. We further show that H1 and Replication Protein A occupy separate nuclear regions, but that H1 colocalizes with the replication factor Proliferating Cell Nuclear Antigen, particularly after DNA damage. Overall, our results provide a refined perspective on the diverse roles of H1 in genome organization and maintenance, and indicate its involvement at stalled replication forks. |
| DOI | 10.1038/s41594-022-00760-4 |
| PubMed ID | 35484234 |
| PubMed Central ID | PMC9117509 |