Polymorphism of Histone Tail Interactions in Nucleosome

Abstract

Histone tails protruding from nucleosome core are known to play important role in gene expression regulation. They affect nucleosome dynamics and remodeling, chromatin compaction, transcription initiation and elongation and serve as targets for multiple posttranslational modifications, known as histone-code. The disordered nature of histone tails makes their structural characterization elusive. To address this question for the first time we perform extensive microsecond molecular dynamics simulations of nucleosome including linker DNA in explicit solvent in order to analyze the evolution of histone tails’ conformation and their interaction patterns with nucleosome core and linker DNA. We show that histone tails readily bind to nucleosomal DNA and become kinetically trapped in a certain number of distinct conformational states at microsecond timescale. Certain bound states of histone tails are associated with secondary structure formation, rearrangement of DNA conformation and protein DNA-interactions in the nucleosome core as well as neutralization of linker DNA. The implications of our findings for nucleosome dynamics, chromatin fiber compaction and histone code functioning are discussed.