Recognition of Nucleosomes by Chromatin Factors: Lessons from Data-Driven Docking-Based Structures of Nucleosome-Protein Complexes

The function of chromatin ultimately depends on the many chromatin-associated proteins
and protein complexes that regulate all DNA-templated processes such as transcription,
repair and replication. As the molecular docking platform for these proteins, the nucleosome is the essential gatekeeper to the genome. As such, the nucleosome-binding activity
of a myriad of proteins is essential for a healthy cell. Here, we review the molecular
basis of nucleosome-protein interactions and classify the different binding modes available. The structural data needed for such studies not only come from traditional sources
such as X-Ray crystallography but also increasingly from other sources. In particular, we
highlight how partial interaction data, derived from for example NMR or mutagenesis,
are used in data-driven docking to drive the modeling of the complex into an atomistic
structure. This approach has opened up detailed insights for several nucleosome-protein
complexes that were intractable or recalcitrant to traditional methods. These structures
guide the formation of new hypotheses and advance our understanding of chromatin
function at the molecular level.