Unspinning chromatin: Revealing the dynamic nucleosome landscape by NMR

Abstract

NMR is an essential technique for obtaining information at atomic resolution on the structure, motions and interactions of biomolecules. Here, we review the contribution of NMR to our understanding of the fundamental unit of chromatin: the nucleosome. Nucleosomes compact the genome by wrapping the DNA around a protein core, the histone octamer, thereby protecting genomic integrity. Crucially, the imposed barrier also allows strict regulation of gene expression, DNA replication and DNA repair processes through an intricate system of histone and DNA modifications and a wide range of interactions between nucleosomes and chromatin factors. In this review, we describe how NMR has contributed to deciphering the molecular basis of nucleosome function. Starting from pioneering studies in the 1960s using natural abundance NMR studies, we focus on the progress in sample preparation and NMR methodology that has allowed high-resolution studies on the nucleosome and its subunits. We summarize the results and approaches of state-of-the-art NMR studies on nucleosomal DNA, histone complexes, nucleosomes and nucleosomal arrays. These studies highlight the particular strength of NMR in studying nucleosome dynamics and nucleosome-protein interactions. Finally, we look ahead to exciting new possibilities that will be afforded by on-going developments in solution and solid-state NMR. By increasing both the depth and breadth of nucleosome NMR studies, it will be possible to offer a unique perspective on the dynamic landscape of nucleosomes and its interacting proteins.