Exploring Interactions of Nucleosome via Interactome Analysis and Integrative Modeling

Abstract

Interactions between nucleosome and various chromatin factors play key role in chromatin regulation such as histone modification and chromatin remodeling. Taking advantage of advances in a number of experimental techniques such as cro-EM, NMR and crosslinking mass spectrometry, we constructed three comprehensive human nucleosome interactomes using high-resolution experimental structures from PDB, recent crosslinking mass spectrometry data in human nuclei and experimental data form APID database. We explored the interactions of nucleosomes with binding partners via network analysis at different levels of details including residue-level, domain-level and protein-level. Residue level interactome allowed us to identify well-defined binding hotspots on histones and nucleosomal DNA. In addition, we performed extensive all atom molecular dynamic simulations to explore the histone tail dynamics and conformations in the context of nucleosomes with linker DNA. Histone tails were found to interact with nucleosomal DNA and histones via preferred binding modes affecting DNA solvent accessibility and thus potentially competing with other nucleosome binding partners.