Highly disordered histone H1-DNA model complexes and their condensates.

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Turner, Abigail L 
Watson, Matthew 
Wilkins, Oscar G 
Cato, Laura 
Travers, Andrew 

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, histone H1, intrinsic disorder, phase separation, phosphorylation, Animals, Chromatin, Chromatin Assembly and Disassembly, DNA, DNA-Binding Proteins, Histones, Humans, Magnetic Resonance Spectroscopy, Nucleic Acid Conformation, Phosphorylation, Protein Binding, Protein Conformation, Protein Processing, Post-Translational
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Proc Natl Acad Sci U S A
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Proceedings of the National Academy of Sciences
Biotechnology and Biological Sciences Research Council (BB/N022181/1)