Set correct time tails full#

However, there is growing evidence that histone tails can extensively interact with the nucleosomal and linker DNA 11, 12, 13, 14, 15, 16, 17, 18, 19, which raises the possibility that tails may modulate the nucleosomal and linker DNA accessibility and regulate the nucleosome recognition by binding partners. Histone tails have a high degree of conformational flexibility and might protrude into the solvent and remain perpetually accessible for binding by chromatin factors 1, 8, 9, 10. Moreover, histone tails may contribute to the inter-nucleosomal interactions and affect the higher-order chromatin structure 5, 6, 7. Intrinsically disordered histone tails flanking histone core domains play particularly important roles, and experiments show that deletions of histone tails may result in the transient unwrapping of DNA, an increase in the nucleosome sliding rate, and a decrease in nucleosome stability 2, 3, 4. Nucleosomes represent the basic subunits of chromatin structure and comprise a histone octamer of four types of core histones, two copies each (H2A, H2B, H3, and H4) and ~147 bp of DNA wrapped around them 1. These seemingly contradictory tasks of DNA packaging and DNA access have been of tremendous research interest. In eukaryotic cells, DNA is packaged in the form of chromatin and should be dynamically accessed during transcription and replication processes with high spatiotemporal precision. Finally, we demonstrate the crosstalk between different histone tail post-translational modifications and mutations those which change charge, suppress tail-DNA interactions and enhance histone tail dynamics and DNA accessibility. These findings are explained within competitive binding and tail displacement models. Using a comprehensive set of experimental nucleosome complexes, we find that the majority of them target mutually exclusive regions with histone tails on nucleosomal/linker DNA around the super-helical locations ± 1, ± 2, and ± 7, and histone tails H3 and H4 contribute most to this process. Different histone types exhibit distinct binding modes to specific DNA regions. We observe rapid conformational transitions between tail bound and unbound states, and characterize kinetic and thermodynamic properties of histone tail-DNA interactions.

Set correct time tails full#

Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full nucleosome, totaling 65 microseconds of molecular dynamics simulations. Little is known about the roles of histone tails in modulating nucleosomal DNA accessibility and its recognition by other macromolecules.