**1. Introduction**

The packaging of DNA into chromatin represents one of the most fundamental layers of the biology of the cell. It provides the required structural compaction of DNA to fit in the nucleus

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and plays crucial roles in controlling cell fate and protecting genome integrity. The fundamental unit of chromatin is the nucleosome in which 147 base pairs (bp) of DNA are wrapped around an octameric protein complex composed of two copies of histone proteins H2A, H2B, H3 and H4 [1–3]. Nucleosomes are arranged as beads-on-a-string forming 10 nanometer (nm) wide fiber that subsequently condense into higher order structures [4]. Nucleosomes as the basis of chromatin are responsible for its dynamics. Chromatin state and changes in DNA accessibility are determined at the nucleosome level. These changes are mediated through interactions of histone proteins and nucleosomal DNA alike with a wide range of protein complexes that control the structure of chromatin. They interpret, write and erase posttranslational modifications or act as ATP-dependent nucleosome remodelers. This allows changes in the functional state of chromatin and regulation of DNA-templated processes. While promoting a large variety of effects on chromatin structure, nucleosome-interacting proteins share the molecular basis of recognizing and binding the nucleosome. Understanding the basis of chromatin dynamics therefore demands understanding the molecular basis of nucleosome-protein interactions.

In particular, insights into the molecular mechanistic basis of how histone-modifying enzymes install or remove post-translational modifications (writers and erasers, respectively) and how these modifications are recognized by effector proteins (readers) are of immense interest, especially in drug development. Deregulation of these proteins is strongly connected to pathological outcome, including cardiovascular diseases, neurological disorders, metabolic disorders and cancer [5]. So-called epigenetic drugs that target the nucleosome interaction of these chromatin factors offer new therapeutic potential [6–9]. A selection of epigenetic drugs including those currently undergoing clinical trial is described in detail elsewhere [10]. Advancement in their development requires insights into the underlying molecular mechanism of nucleosome recognition, enabling control over subsequent modification of the chromatin state.

In the following, we will review the molecular basis of nucleosome-protein interactions, focusing on the different binding epitopes presented by the nucleosome. After an overview of the nucleosome-protein structures determined by crystallography or cryo-electron microscopy (cryo-EM), we highlight several studies in which experimental data from nuclear magnetic resonance spectroscopy (NMR), cross-link-based mass spectrometry (XL-MS) or mutational analysis were used to build atomistic structural models of nucleosome complexes. Throughout, we emphasize the role of these data-driven models in deepening our understanding of nucleosome recognition.
