Beyond the Nucleosome: Nucleosome-Protein Interactions and Higher Order Chromatin Structure

The regulation of chromatin biology ultimately depends on the manipulation of its smallest subunit, the nucleosome. The proteins that bind and operate on the nucleosome do so, while their substrate is part of a polymer embedded in the dense nuclear environment. Their molecular interactions must in some way be tuned to deal with this complexity. Due to the rapid increase in the number of high-resolution structures of nucleosome-protein complexes and the increasing understanding of the cellular chromatin structure, it is starting to become clearer how chromatin factors operate in this complex environment. In this review, we analyze the current literature on the interplay between nucleosome-protein interactions and higher-order chromatin structure. We examine in what way nucleosomes-protein interactions can affect and can be affected by chromatin organization at the oligonucleosomal level. In addition, we review the characteristics of nucleosome-protein interactions that can cause phase separation of chromatin. Throughout, we hope to illustrate the exciting challenges in characterizing nucleosome-protein interactions beyond the nucleosome. (C) 2021 The Author(s). Published by Elsevier Ltd.

Automated summary

The regulation of chromatin biology relies heavily on manipulating the smallest subunit, the nucleosome, and molecular interactions must be tuned to navigate the complexity of the dense nuclear environment. This review analyzes the interplay between nucleosome-protein interactions and higher-order chromatin structure, shedding light on how these factors operate in a complex environment. Additionally, characteristics of nucleosome-protein interactions that can lead to phase separation of chromatin are reviewed, highlighting the challenges in characterizing interactions beyond the nucleosome.