Recognition of the nucleosome by chromatin factors and enzymes

Abstract

Dynamic expression of the genome requires coordinated binding of chromatin factors and enzymes that carry out genome-templated processes. Until recently, the molecular mechanisms governing how these factors and enzymes recognize and act on the fundamental unit of chromatin, the nucleosome core particle, have remained a mystery. A small, yet growing set of structures of the nucleosome in complex with chromatin factors and enzymes highlights the importance of multivalency in defining nucleosome binding and specificity. Many such interactions include an arginine anchor motif, which targets a unique acidic patch on the nucleosome surface. These emerging paradigms for chromatin recognition will be discussed, focusing on several recent structural breakthroughs.

Figure 1

Nucleosome core particle structure. Different surface representations of the nucleosome core particle structure (PDB ID: 1KX5) highlighting (a) individual histone proteins (H3, H4, H2A, and H2B colored blue, green, yellow, and red, respectively) and DNA (light blue), (b) the histone core (blue) and histone tails (green), (c) the nucleosome as single binding surface and (d) electrostatic surface of nucleosome core particle with histone H2A/H2B dimer acidic patch indicated. Electrostatic representation generated with ABPS [58]. All figures in this manuscript were prepared with PyMOL software [57].

Figure 2

Recent chromatin factor-nucleosome core particle structures. (a) Orthogonal views of PRC1 ubiquitylation module-nucleosome core particle structure, left and center, and footprint of PRC1 on nucleosome surface colored by interacting components of PRC1, right. The Cα atom of the PRC1 targeted residue of H2A (Lys119) is represented by an orange sphere. (b) Similar views of chromatosome structure with the globular domain of H5. (c) Orthogonal views of intasome-nucleosome docking model. Integrase subunits shown in yellow, orange, green and dark green with outer subunits in darker shades. Integrase DNA colored blue. Nucleosome footprint not shown for intasome due to resolution of this model. H3, H4, H2A, H2B and nucleosomal DNA colored light blue, light green, pink, light yellow, and light blue respectively.

Figure 3

The arginine anchor motif. Side chains of arginine anchor residues from RCC1, Sir3, PRC1 (Ring1B), LANA, and CENP-C shown in surface representation with side chains from acid triad of H2A in stick representation. Nucleosomal DNA shown as sticks.