Intra- and inter-nucleosome interactions of the core histone tail domains in higher-order chromatin structure

Abstract

Eukaryotic chromatin is a hierarchical collection of nucleoprotein structures that package DNA to form chromosomes. The initial levels of packaging include folding of long strings of nucleosomes into secondary structures and array-array association into higher-order tertiary chromatin structures. The core histone tail domains are required for the assembly of higher-order structures and mediate short- and long-range intra- and inter-nucleosome interactions with both DNA and protein targets to direct their assembly. However, important details of these interactions remain unclear and are a subject of much interest and recent investigations. Here, we review work defining the interactions of the histone N-terminal tails with DNA and protein targets relevant to chromatin higher-order structures, with a specific emphasis on the contributions of H3 and H4 tails to oligonucleosome folding and stabilization. We evaluate both classic and recent experiments determining tail structures, effect of tail cleavage/loss, and posttranslational modifications of the tails on nucleosomes and nucleosome arrays, as well as inter-nucleosomal and inter-array interactions of the H3 and H4 N-terminal tails.

Figure 1. The histone fold domains and N-terminal tails

A. Cartoon of the histone fold domains (grey boxes) and tail domains (dashed lines) within a linear map of the core histones. α-helicies are indicated by columns. The positions of residues flanking the histone fold in each protein are indicated. The approximate residue at the end of the tail domain nearest the histone fold is also indicated. B. Cartoon of the nucleosome showing histone fold domains (colors correspond to A) and N-terminal tail domains extending away from the nucleosome core. Note that H2A also has a C-terminal tail. Basic residues (lysines and arginines) in the tail domains are colored red. Sites of lysine acetylation are indicated by a star. Figure adapted from (Wolffe and Hayes 1999).

Figure 2. Salt-dependent folding and condensation of model nucleosome arrays

A model nucleosome array is reconstituted from a template containing 12 tandem repeats of a nucleosome positioning sequence and purified core histone proteins (top right). The salt-dependent folding behavior of the arrays is shown, first forming a partially folded ‘contacting zig-zag’ structure in low Mg²⁺ and a fully condensed structure in higher salt that has the same hydrodynamic shape as a 30 nm-diameter chromatin fiber. Additional increases in salt induce self-association of arrays to form tertiary chromatin structures (bottom, left). Array folding is facilitated by inter-nucleosome, intra-array interactions while self-association is driven in part by inter-nucleosome, inter-array contacts (see inset).