Highly disordered histone H1-DNA model complexes and their condensates.
Turner, Abigail L
Wilkins, Oscar G
Proc Natl Acad Sci U S A
Proceedings of the National Academy of Sciences
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Turner, A. L., Watson, M., Wilkins, O. G., Cato, L., Travers, A., Thomas, J., & Stott, K. (2018). Highly disordered histone H1-DNA model complexes and their condensates.. Proc Natl Acad Sci U S A, 115 (47), 11964-11969. https://doi.org/10.1073/pnas.1805943115
Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.
Chromatin, Animals, Humans, DNA-Binding Proteins, Histones, DNA, Magnetic Resonance Spectroscopy, Chromatin Assembly and Disassembly, Protein Processing, Post-Translational, Nucleic Acid Conformation, Protein Conformation, Protein Binding, Phosphorylation
Biotechnology and Biological Sciences Research Council (BB/N022181/1)
External DOI: https://doi.org/10.1073/pnas.1805943115
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285594