Molecular recognition of nucleosomes by binding partners

Abstract

Nucleosomes represent the elementary units of chromatin packing and hubs in epigenetic signaling pathways. Across the chromatin and over the lifetime of the eukaryotic cell, nucleosomes experience a broad repertoire of alterations that affect their structure and binding with various chromatin factors. Dynamics of the histone core, nucleosomal and linker DNA, and intrinsic disorder of histone tails add further complexity to the nucleosome interaction landscape. In light of our understanding through the growing number of experimental and computational studies, we review the emerging patterns of molecular recognition of nucleosomes by their binding partners and assess the basic mechanisms of its regulation.

Figure 1.. Growth trends in the number of nucleosome structures.

Blue graph shows the cumulative number of NCP structures in the PDB while the green graph shows the structures of the NCP in complex with a protein or peptide. From left to right, insets illustrate the first nucleosome crystal structure (1AOI, [1]), Sir3 BAH domain bound to yeast nucleosome (3TU4, [64]) and RNA Polymerase II elongation complex stalled at nucleosomal DNA SHL-2 (6A5R, [65]).

Figure 2.. Features of the nucleosomal recognition.

Nucleosome binding partners are shown in orange and specific examples are given in parentheses. A. Multivalent recognition of the nucleosome (from left to right): through multiple histones (Sir3 BAH domain, [64]), via specific histone variants and nucleosomal DNA (CENP-N bound to centromeric nucleosome [66]), through multiple modifications (53BP1, [27]), multiple geometric cues or periodic patterns (transcription factors [19]). B. A binding partner recognizes variant nucleosome and does not recognize canonical nucleosome or free histones (ATXR5, [3]). C. Multiple modifications can antagonistically influence the recognition by binding partner (Fdxl11/KDM2A, [11]). D. Multiple modifications and histone variants can have opposing effects on nucleosome dynamics with consequences for recognition ([28]). E. Competitive binding between core histone tails, H1, linker DNA and histone modifications ([45]).

Figure 3.. Interactions between the basic patch within the histone H4 tail and acidic binding pockets of chromatin remodelers.

A. Snf2 (5X0Y [5]), B. Chd1 (5O9G [6]). Molecular surfaces are rendered in orange (Snf2 or Chd1), blue (H3), green (H4), yellow (H2A), red (H2B), and brown (DNA), respectively. Insets show the electrostatic potential mapped of the remodelers’ molecular surfaces. H4 sidechains on the binding interface are labeled.