The HMGN family of chromatin-binding proteins: dynamic modulators of epigenetic processes

Abstract

The HMGN family of proteins binds to nucleosomes without any specificity for the underlying DNA sequence. They affect the global and local structure of chromatin, as well as the levels of histone modifications and thus play a role in epigenetic regulation of gene expression. This review focuses on the recent studies that provide new insights on the interactions between HMGN proteins, nucleosomes, and chromatin, and the effects of these interactions on epigenetic and transcriptional regulation. This article is part of a Special Issue entitled: Chromatin in time and space.

Figure 1. Functional domains of of HMGN proteins and a model of the HMGN2-CP complex

(a) Domain structure of HMGN proteins. All HMGN proteins contain three functional domains: a bipartite nuclear localization signal (NLS, shown in blue, a nucleosome binding domain, NBD, shown in red, and a C-terminal regulatory domain, RD, shown in black). The core binding domain within the NBD is indicated, and the four amino-acids essential for nucleosome binding are shown in red. (b) The HMGN2-core particle complex. One HMGN2 molecule binds to each side of the nucleosome core with its NBD domain. The highly conserved core of the NBD interacts with an acidic patch formed by histone H2A and H2B, while the C-terminal portion interacts with the DNA near or at the two major groves flanking the nucleosomal dyad axis. The binding of an HMGN to the nucleosome places the C-terminal tail of that HMGN near the site where the linker DNA exits and enter the CP, potentially affecting the binding of linker histone H1 to this region [48, 49]. This model supports earlier results that the N-terminal domain of HMGN targets a restricted region in histone H2B, whereas the C-terminal domain targets a restricted region in the N terminus of histone H3 (dotted oval). In addition, it also supports previous conclusions that HMGNs protect the ends of DNA flanking the nucleosomal dyad axis. Modified from [19].

Figure 2. A model for the dynamic modulation of chromatin structure by HMGNs

In living cells, HMGN proteins compete with linker histone H1 and bind dynamically to nucleosomes. HMGNs also interact with histone H3 and H4 tails. The C-terminal domain of HMGNs interacts with the N-terminal of histone H3, and the interaction of the NBD with the acidic patch in the histone octamer competes with the binding of the N-terminal of H4 from a neighboring nucleosome. The overall effect of HMGN binding is chromatin decompaction.